Umeå universitets logga

umu.sePublikationer
Ändra sökning
Avgränsa sökresultatet
12 1 - 50 av 65
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Ahmadi, Mahboobah
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Liu, Jing-Xia
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Stål, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Human extraocular muscles in ALS2010Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 51, nr 7, s. 3494-3501Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. To investigate the general morphology, fiber type content, and myosin heavy chain (MyHC) composition of extraocular muscles (EOMs) from postmortem donors with amyotrophic lateral sclerosis (ALS) and to evaluate whether EOMs are affected or truly spared in this disease. METHODS. EOM and limb muscle samples obtained at autopsy from ALS donors and EOM samples from four control donors were processed for immunohistochemistry with monoclonal antibodies against distinct MyHC isoforms and analyzed by SDS-PAGE. In addition, hematoxylin and eosin staining and nicotinamide tetrazolium reductase (NADH-TR) activity were studied. RESULTS. Wide heterogeneity was observed in the appearance of the different EOMs from each single donor and between donors, irrespective of ALS type or onset. Pathologic morphologic findings in ALS EOMs included presence of atrophic and hypertrophic fibers, either clustered in groups or scattered; increased amounts of connective tissue; and areas of fatty replacement. The population of fibers stained with anti-MyHCslow tonic was smaller than that of MyHCIpositive fibers and was mostly located in the orbital layer in most of the ALS EOM samples, whereas an identical staining pattern for both fiber populations was observed in the control specimens. MyHCembryonic was notably absent from the ALS EOMs. CONCLUSIONS. The EOMs showed signs of involvement with altered fiber type composition, contractile protein content, and cellular architecture. However, when compared to the limb muscles, the EOMs were remarkably preserved. EOMs are a useful model for the study of the pathophysiology of ALS.

  • 2.
    Ambarki, Khalid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hallberg, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Lindén, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Zarrinkoob, Laleh
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Blood flow of ophthalmic artery in healthy individuals determined by phase-contrast magnetic resonance imaging2013Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 54, nr 4, s. 2738-2745Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: Recent development of magnetic resonance imaging (MRI) offers new possibilities to assess ocular blood flow. This prospective study evaluates the feasibility of phase-contrast MRI (PCMRI) to measure flow rate in the ophthalmic artery (OA) and establish reference values in healthy young (HY) and elderly (HE) subjects.

    METHODS: Fifty HY subjects (28 females, 21-30 years of age) and 44 HE (23 females, 64-80 years of age) were scanned on a 3-Tesla MR system. The PCMRI sequence had a spatial resolution of 0.35 mm per pixel, with the measurement plan placed perpendicularly to the OA. Mean flow rate (Qmean), resistive index (RI), and arterial volume pulsatility of OA (ΔVmax) were measured from the flow rate curve. Accuracy of PCMRI measures was investigated using a vessel-phantom mimicking the diameter and the flow rate range of the human OA.

    RESULTS: Flow rate could be assessed in 97% of the OAs. Phantom investigations showed good agreement between the reference and PCMRI measurements with an error of <7%. No statistical difference was found in Qmean between HY and HE individuals (HY: mean ± SD = 10.37 ± 4.45 mL/min; HE: 10.81 ± 5.15 mL/min, P = 0.655). The mean of ΔVmax (HY: 18.70 ± 7.24 μL; HE: 26.27 ± 12.59 μL, P < 0.001) and RI (HY: 0.62 ± 0.08; HE: 0.67 ± 0.1, P = 0.012) were significantly different between HY and HE.

    CONCLUSIONS: This study demonstrated that the flow rate of OA can be quantified using PCMRI. There was an age difference in the pulsatility parameters; however, the mean flow rate appeared independent of age. The primary difference in flow curves between HE and HY was in the relaxation phase of the systolic peak.

  • 3. Behndig, A
    et al.
    Karlsson, K
    Johansson, B O
    Brännström, T
    Marklund, S L
    Superoxide dismutase isoenzymes in the normal and diseased human cornea.2001Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 42, nr 10, s. 2293-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: The human cornea, a tissue much exposed to oxidative stress, is rich in extracellular superoxide dismutase (SOD). In this study, the contents and distributions of the SOD isoenzymes in the normal human cornea were compared with those in corneas affected by keratoconus and bullous keratopathy.

    METHODS: The central and peripheral parts of normal human corneas were analyzed separately. Central corneal buttons were obtained from patients with keratoconus and bullous keratopathy who were undergoing primary keratoplasty or retransplantation. SOD enzymatic activities were determined by a direct spectrophotometric method, and extracellular SOD and the cytosolic Cu- and Zn-containing SOD (CuZn-SOD) proteins were determined with ELISA and studied with immunohistochemistry.

    RESULTS: The total SOD content, and particularly the extracellular SOD content, was lower in the central than in the peripheral normal cornea. CuZn-SOD and extracellular SOD were demonstrated in all three corneal layers. CuZn-SOD was found in cells, whereas extracellular SOD appeared to be localized on cell surfaces, in basal membranes, and in the stroma. In keratoconus, corneal levels of extracellular SOD were half those in the control corneas, whereas CuZn-SOD and the mitochondrial Mn-containing SOD levels were normal. In bullous keratopathy, apart from edematous dilution, SOD isoenzyme levels were essentially normal. In a remarkable finding, the same pattern in SOD isoenzyme levels as in the original disease was also found at retransplantation.

    CONCLUSIONS: Extracellular SOD and CuZn-SOD show markedly different distribution patterns within the human cornea. Extracellular SOD activity in the central cornea is halved in keratoconus, compared with that in normal control corneas. The finding of a similar reduction at retransplantation in keratoconus suggests reduced corneal extracellular SOD synthesis in cells of the host as a cause of the low enzyme levels.

  • 4.
    Behzadi, Arvin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Tjust, Anton Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Liu, Jing-Xia
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Andersen, Peter Munch
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. https://orcid.org/0000-0002-4201-8204.
    Pedrosa Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Myofiber type shift in extraocular muscles in amyotrophic lateral sclerosis2023Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 64, nr 5, artikel-id 15Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To investigate changes in myofiber composition in the global layer (GL) and orbital layer (OL) of extraocular muscles (EOMs) from terminal amyotrophic lateral sclerosis (ALS) donors.

    Methods: Medial recti muscles collected postmortem from spinal-onset ALS, bulbar-onset ALS, and healthy control donors were processed for immunofluorescence with antibodies against myosin heavy chain (MyHC) IIa, MyHCI, MyHCeom, laminin, neurofilaments, synaptophysin, acetylcholine receptor γ-subunit, and α-bungarotoxin.

    Results: The proportion of myofibers containing MyHCIIa was significantly smaller and MyHCeom was significantly larger in the GL of spinal-onset ALS and bulbar-onset ALS donors compared to control donors. Changes in the GL were more prominent in the bulbar-onset ALS donors, with a significantly larger proportion of myofibers containing MyHCeom being present compared to spinal-onset ALS donors. There were no significant differences in the myofiber composition in the OL. In the spinal-onset ALS donors, the proportions of myofibers containing MyHCIIa in the GL and MyHCeom in the OL were significantly correlated with the disease duration. Neurofilament and synaptophysin were present at motor endplates of myofibers containing MyHCeom in ALS donors.

    Conclusions: The EOMs of terminal ALS donors displayed changes in the fast-type myofiber composition in the GL, with a more pronounced alteration in bulbar-onset ALS donors. Our results align with the worse prognosis and subclinical changes in eye movement function previously observed in bulbar-onset ALS patients and suggest that the myofibers in the OL might be more resistant to the pathological process in ALS.

    Ladda ner fulltext (pdf)
    fulltext
  • 5.
    Borbely, Gabor
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Löfgren, Filip
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Sloniecka, Marta
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Backman, Ludvig J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    The role of neurokinin A in corneal wound repair2015Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, nr 7, artikel-id Meeting Abstract: 725Artikel i tidskrift (Övrigt vetenskapligt)
  • 6.
    Burstedt, Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Jonsson, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Westin, Ida Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Phenotypic expression of EYS mutations in patients with autosomal recessive retinitis pigmentosa in northern Sweden2018Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, nr 9Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Purpose : To describe clinical phenotype in patients of northern Sweden affected by recessive retinitis pigmentosa (ARRP) caused by mutations in Eyes Shut Homolog (Drosophila) (EYS) gene.

    Methods : Whole exome sequencing (WES) and multiple ligation dependent prode amplification (MLPA) were used for identification of EYS sequence variants in a cohort of ARRP patients (n=148) from northern Sweden. The patients with EYS mutations were ophthalmologically examined over time using visual acuity (ETDRS), visual fields, slit lamp and fundus examination and ocular coherence tomography (OCT). Dark adaptometry and full-field electroretionograms (ERG) was performed.

    Results : Phenotype characterization was done in 13 ARRP cases with EYS mutations representing five bi-allelic sequence variants, three of which were novel. Only one variant was detected in two cases. The phenotypic outcome was predominately presented as classical RP aggravating in young adulthood. However, among these patients we observed a variation of phenotypic expression with initial paracentral to central macular affection of the retina and areolar retinal degeneration with electrophysiological outcome of only slightly subnormal responses of both rods and cones in late adulthood (60 y/o), clinically defined as areolar atrophy.

    Conclusions : The EYS mutations account for 10% of ARRP in northern Sweden. The phenotype presents both typical classical RP and chorioretinal degenerative retinal disease, areolar dystrophy. This suggests that molecular genetic testing of the EYS is crucial when both RP and pattern macular diseases are clinically diagnosed.

  • 7.
    Burstedt, Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Whelan, James H.
    Memorial University of Newfoundland, St John's, Newfoundland, Canada.
    Green, Jane S.
    Memorial University of Newfoundland, St John's ,Newfoundland, Canada.
    Holopigian, Karen
    Novartis Institutes for BioMedical Research, NJ, East Hanover, United States.
    Spera, Claudio
    Novartis Pharma AG, Basel, Switzerland.
    Greco, Erin
    Novartis Institutes for BioMedical Research, MA, Cambridge, United States.
    Deslandes, Jean-Yves
    Novartis Institutes for BioMedical Research, NJ, East Hanover, United States.
    Wald, Michael
    Novartis Institutes for BioMedical Research, MA, Cambridge, United States.
    Grosskreutz, Cynthia
    Novartis Institutes for BioMedical Research, MA, Cambridge, United States.
    Ni, Xiao
    Novartis Institutes for BioMedical Research, MA, Cambridge, United States.
    Normand, Guillaume
    Novartis Institutes for BioMedical Research, NJ, East Hanover, United States.
    Maker, Michael
    Novartis Institutes for BioMedical Research, NJ, East Hanover, United States.
    Charil, Arnaud
    Novartis Institutes for BioMedical Research, MA, Cambridge, United States.
    Rosol, Michael
    Novartis Institutes for BioMedical Research, MA, Cambridge, United States.
    He, Yunsheng
    Novartis Institutes for BioMedical Research, MA, Cambridge, United States.
    Stasi, Kalliopi
    Novartis Institutes for BioMedical Research, MA, Cambridge, United States.
    Retinal dystrophy associated with RLBP1 retinitis pigmentosa: a five-year prospective natural history study2023Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 64, nr 13, artikel-id 42Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To assess the progression in functional and structural measures over a five-year period in patients with retinal dystrophy caused by RLBP1 gene mutation.

    Methods: This prospective, noninterventional study included patients with biallelic RLBP1 mutations from two clinical sites in Sweden and Canada. Key assessments included ocular examinations, visual functional measures (best-corrected visual acuity [BCVA], contrast sensitivity [CS], dark-adaptation [DA] kinetics up to six hours for two wavelengths [450 and 632 nm], Humphrey visual fields [HVF], full-field flicker electroretinograms), and structural ocular assessments.

    Results: Of the 45 patients enrolled, 38 completed the full five years of follow-up. At baseline, patients had BCVA ranging from -0.2 to 1.3 logMAR, poor CS, HVF defects, and prominent thinning in central foveal thickness. All patients had extremely prolonged DA rod recovery of approximately six hours at both wavelengths. The test-retest repeatability was high across all anatomic and functional endpoints. Cross-sectionally, poorer VA was associated with older age (right eye, correlation coefficient [CC]: 0.606; left eye, CC: -0.578; P < 0.001) and HVF MD values decreased with age (right eye, CC: -0.672, left eye, CC: -0.654; P < 0.001). However, no major changes in functional or structural measures were noted longitudinally over the five-year period.

    Conclusions: This natural history study, which is the first study to monitor patients with RLBP1 RD for five years, showed that severely delayed DA sensitivity recovery, a characteristic feature of this disease, was observed in all patients across all age groups (17-69 years), making it a potentially suitable efficacy assessment for gene therapy treatment in this patient population.

    Ladda ner fulltext (pdf)
    fulltext
  • 8.
    Byström, Berit
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Carracedo, Sergio
    Behndig, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Gullberg, Donald
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Alpha11 integrin in the human cornea: importance in development and disease.2009Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 50, nr 11, s. 5044-5053Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To examine the distribution of the alpha11 integrin chain in the human cornea during fetal development and in normal and diseased adult human corneas.

    METHODS: Six fetal corneas, 10 to 20 weeks of gestation (wg), and 18 adult corneas including 3 normal, 7 with keratoconus, 5 with pseudophakic bullous keratopathy (PBK), 2 with Fuchs' corneal dystrophy, and 1 with a scar after deep lamellar keratoplasty (DLKP) were processed for immunohistochemistry with specific antibodies against the alpha11 integrin chain; collagen I, IV, and V; and alpha-smooth muscle actin (alpha-SMA). The cellular source of alpha11 integrin chain was further investigated in cell cultures.

    RESULTS: At 10 to 17 wg, the alpha11 integrin chain was predominantly present in the anterior corneal stroma. At 20 wg, in normal adult corneas and in Fuchs' dystrophy corneas there was weak staining in the stroma. The PBK corneas showed variable and weak staining, generally accentuated in the posterior stroma near Descemet's membrane. In contrast, the anterior portion of the stroma in the keratoconus corneas was strongly stained in an irregular streaky pattern. Human corneal fibroblasts/myofibroblasts produced alpha11 integrin chain in culture. Cultures treated with TGF-beta showed higher content of both alpha-SMA and the alpha11 integrin chain.

    CONCLUSIONS: The presence of the alpha11 integrin chain during early corneal development and the enhanced expression in scarred keratoconus corneas indicates that this integrin chain is likely to play an important role in collagen deposition during corneal development and in keratoconus with a scarring component and compromised basement membrane integrity.

  • 9.
    Byström, Berit
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Vicente, André
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Domellöf, Fatima Pedrosa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Notch1 Signaling Pathway in Aniridia- Related Keratopathy, Normal Fetal and Adult Human Corneas2018Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, nr 9Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Purpose : Notch1 is suggested to play an important role during tissue development and in differentiation of the corneal epithelial cells whereas its inhibitors Dlk1 and Numb keep these cells in an immature status. Our purpose was to evaluate the presence of these factors in aniridia-related keratopathy (ARK) and in normal fetal and adult human corneas.

    Methods : Two human fetal corneas, 10 and 20 weeks of gestation, two naïve corneal buttons from patients with advanced ARK, three corneal buttons from patients with ARK undergoing re-transplantation, as well as two adult healthy control corneas were processed for immunohistochemistry using antibodies against Notch1, Dlk1 and Numb.

    Results : Identical staining patterns were found for Notch1 in normal adult and fetal corneas, with staining around the basal epithelial cells and in a few streaks in the stroma. In ARK corneas, Notch1 was not detected in the pannus of the stroma. On the contrary, the pannus in ARK was labeled with antibodies against Dlk1. Dlk1 was also abundant in the epithelium and in the stroma of fetal corneas but was absent from the stroma of normal adult corneas. Numb was present in the adult normal corneas and in addition labeled the ARK and fetal corneas in a pattern resembling that of Dlk1.

    Conclusions : The lack of Notch1 together with abundant Dlk1 and Numb, suggest a disturbed balance between these important factors in ARK, likely to hamper differentiation of the progenitor cell population and to be important for the pathophysiology of ARK.

  • 10.
    Byström, Berit
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Virtanen, Ismo
    Rousselle, Patricia
    Gullberg, Donald
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Distribution of laminins in the developing human eye2006Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 47, nr 3, s. 777-785Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To examine the distribution of laminin (Ln) chains in basement membranes (BMs) of the human cornea, lens, and retina in fetal development. METHODS: Ten fetal eyes (9-20 weeks of gestation [wg]) were serially sectioned and treated with specific antibodies against the Ln-alpha1, -alpha2, -alpha3, -alpha4, -alpha5, -beta1, -beta2, -beta3, and -gamma1 chains. RESULTS: The BM of the corneal epithelium was reactive for Ln-alpha3, -alpha5, -beta1, and beta3 chains through all ages, whereas the Ln-alpha1 chain was present at 9 to 12 wg and the Ln-alpha4 chain from 10 wg. The Descemet's membrane (DM) was labeled with the Ln-alpha1 and -alpha4 chains at 10 to 17 wg, the Ln-alpha5 chain from 10 wg, the Ln-beta1 chain at 11 to 17 wg, and the Ln-beta3 chain from 17 wg. The Ln-alpha1, alpha5, -beta1, and -beta2 chains were present in the lens capsule and the internal limiting membrane (ILM) through all ages. The Bruch's membrane (BrM) was immunoreactive for the Ln-alpha3, alpha4, -alpha5, -beta1, and -beta2 chains through all ages, whereas the Ln-alpha1 chain was absent from 20 wg onward. The Ln-alpha2 chain was not detected in the eye, but it was present in the extraocular muscles. CONCLUSIONS: BMs play an important role during morphogenesis, in that they influence cell proliferation, migration, and tissue differentiation. Lns are the major noncollagenous component of BMs. The presence of four different alpha chains, three beta chains, and one gamma chain of Ln in the eye reveals a high degree of complexity from the early stages of development and suggests an important role for the different Ln chains in human ocular differentiation.

  • 11. Di, Guohu
    et al.
    Qi, Xia
    Zhao, Xiaowen
    Zhang, Songmei
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Zhou, Qingjun
    Corneal Epithelium-Derived Neurotrophic Factors Promote Nerve Regeneration2017Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 58, nr 11, s. 4695-4702Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. To explore the neurotrophic factor expression in corneal epithelium and evaluate their effects on the trigeminal ganglion (TG) neurite outgrowth and corneal nerve regeneration in mice. METHODS. The expression of neurotrophic factors was compared among the intact, regenerating, and regenerated mouse corneal epithelium. Mouse primary TG neurons were treated with the conditioned medium of mouse corneal epithelial cells. Nerve growth factor (NGF) neutralizing antibody and glial cell-derived neurotrophic factor (GDNF) neutralizing antibody were used to evaluate their roles in mouse corneal nerve regeneration and TG neurite outgrowth. The promoting effects of NGF and GDNF for the corneal nerve regeneration were further evaluated in the diabetic mice. RESULTS. The expression of NGF and GDNF showed significant up-regulation in regenerating corneal epithelium and return to the preinjury levels in the regenerated epithelium, which was consistent with the progress of corneal subbasal nerve regeneration. The conditioned medium of corneal epithelial cells promoted the TG neurite outgrowth with extended branching and elongation. Furthermore, the blockage of either NGF or GDNF significantly impaired the promotion of the neurite outgrowth by the conditioned medium or the corneal nerve regeneration in normal mice. Moreover, the expression of NGF and GDNF was attenuated in the diabetic regenerating corneal epithelium as compared to that in normal mice, while exogenous NGF or GDNF supplement promoted the corneal epithelial and nerve regeneration in diabetic mice. CONCLUSIONS. Corneal epithelium expresses multiple neurotrophic factors, among which NGF and GDNF may play an important role in the corneal nerve regeneration.

  • 12.
    Domellöf, Fatima Pedrosa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Liu, Jing-Xiu
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    The cytoskeleton of myotendinous junctions in human extraocular muscles2020Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 61, nr 7Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Purpose: To systematically investigate the composition of the cytoskeleton of the myotendinous junctions (MTJs) in human extraocular muscles (EOMs).

    Methods: Ten human EOM samples collected with ethical permission were processed for immunofluorescence with antibodies against the cytoskeletal proteins desmin, nestin, vimentin and cytokeratin 19; various myosin heavy chain (MyHC) isoforms as well as antibodies against tenascin or laminin to identify the MTJs.

    Results: The majority of the MTJs in both orbital and global layer contained desmin but an important proportion of them did not show increased levels of immunostaining at the folds of the MTJ, in contrast to other muscles. Desmin was absent from approximately 15% of the MTJs and mostly in myofibers containing MyHCIIa. Nestin was present in approximately 91% of the MTJs. Four different combinations were encountered regarding immunolabeling for desmin+nestin at the MTJs, including absence of both in a subgroup of MTJs, irrespective of fiber type. Vimentin was not present at the MTJs and cytokeratin 19 was either present or absent from the MTJs.

    Conclusions: The present data on the composition of the cytoskeleton at the MTJs in the EOMs raises fundamental questions regarding our previous knowledge on the role of these proteins for force transmission. We propose a novel model to further investigate these questions.

  • 13.
    Domellöf, Fatima Pedrosa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Parkkonen, Kimmo
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Lindström, Mona
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Nord, Hanna
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    von Hoffsten, Jonas
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Li, Zhenlin
    Univ Paris 06, CNRS, INSERM, Inst Biol Paris Seine, Paris, France.
    Desmin in extraocular muscles2015Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, nr 7Artikel i tidskrift (Övrigt vetenskapligt)
  • 14.
    Domellöf, Fatima Pedrosa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Rodriguez Garcia, Maria Angels
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Vicente, André
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Sandgren Hochhard, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Sarcomere remodelling and gene expression profile changes following strabismus surgery2018Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, nr 9Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Purpose : To investigate the extent and time axis of sarcomere remodeling and of gene expression profile changes following resection surgery in an animal model of strabismus surgery.

    Methods : The right superior rectus (SR) of 16 adult New Zealand white rabbits was resected 4 mm and reattached to the sclera, with ethical permission and following the animal care directives. The superior rectus muscle of 4 rabbits was collected 1, 2, 4 and 6 weeks after surgery. The SR of 4 control rabbits was also collected. The muscles were divided into two pieces longitudinally and one half was directly frozen for RNA extraction and the other half was stretched, fixed in 2% paraformaldehyde and frozen after sucrose cryoprotection. Serial longitudinal sections were processed for immunohistochemistry with antibodies against desmin. For each muscle section, the area comprising exclusively longitudinally sectioned myofibers was evaluated and the number of dividing sarcomeres present within that area was determined. RNA sequencing was performed with Illumina HiSeq 2500.

    Results : One week after surgery, the number of sarcomere divisions was 86.5/mm2 (range 30.9-152.7), after two weeks 72.0/ mm2 (42.5-95.9), after 4 weeks 95.7/ mm2 (37.4-161.3). After 6 weeks the number of sarcomere divisions (26.8/ mm2, 9.2-60.7) was similar to that of the control samples (26.0/ mm2, 6.0-66.9). RNA sequencing revealed up to 198 differentially expressed genes and further bioinformatics analysis is ongoing. Preliminary data indicate that the most significantly altered biological processes are those involved in extracellular matrix organization and inflammation, along with regulation of response and production of growth factors involved in muscle repair and regeneration.

    Conclusions : Signs of sarcomerogenesis were present during the first 4 weeks after resection of the superior rectus, suggesting that sarcomerogenesis plays a role in surgical failure due to recovery of muscle length. We suggest that medical approaches to limit this mechanism may be a desirable complementary therapy to strabismus surgery in the future.

  • 15.
    Eklund, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Hallberg, Per
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Lindén, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Lindahl, Olof A.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    An applanation resonator sensor for measuring intraocular pressure using combined continuous force and area measurement2003Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, nr 7, s. 3017-3024Artikel i tidskrift (Refereegranskat)
  • 16. Fast, Elizabeth
    et al.
    Holm, Linus
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    McLoon, Linda K.
    Engel, Stephen
    Eye vergence is limited by adaptation2016Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, nr 12Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose : What limits vergence abilities? Current models propose that vergence movements are controlled by a phasic component, which responds to image disparities, and a slower tonic component that adapts based on the output of the phasic component. Adaptation in the tonic component frees the phasic component to compensate for further image disparities. Limits of vergence should arise when the tonic component can no longer adapt, but this failure has yet to be observed empirically. We tested the hypothesis that vergence limits would arise when there was evidence of a weakening adaptation in the tonic component.

    Methods : We adapted the vergence system of 6 subjects using a Wheatstone stereoscope. Binocular eye position was collected with an Eyelink 1000 eyetracker. Subjects binocularly viewed a detailed image of a natural scene. The image was initially presented at zero disparity, and moved laterally in one eye at a rate of 0.5°/s to reach 4° of eccentricity, where it remained for 5 m. Then the image moved in blocks, where each block comprised 1° of movement followed by 5 m of viewing at the new eccentricity. Blocks repeated until subjects experienced diplopia for 75% of a block. The eyetracker was used to calculate the angle between the eyes optical axes, which we term divergence. Phoria was measured every 30 s by calculating divergence when the image in one eye was replaced with a gray field for 5 s. As a control, subjects also viewed the display with one image moving continuously without the 5 m adaptation periods.

    Results : Subjects were able to fuse the images until eye divergence reached 7.14°, on average. We used phoria to estimate adaptation in the tonic component, with larger phorias indicating less adaptation. Adaptation, as measured by phoria, decreased over successive blocks (linear trend, p < 0.01). In addition, subjects reached a significantly greater divergence with adaptation than in the control condition (5.17°, p = 0.02).

    Conclusions : Our results support the hypothesis that the amount of vergence normal viewers can produce is limited by adaptation in the tonic component. In earlier blocks, when the tonic component adapted more fully, subjects were able to fuse the images, but in later blocks adaptation of the tonic component lagged behind, and diplopia was experienced. Future work can explore how the tonic component could adapt further, allowing the eyes to experience vergence angles unreachable in normal experience.

  • 17.
    Golovleva, Irina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Jonsson, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Burstedt, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Heterogeneity and complexity of EYS mutations in autosomal recessive retinitis pigmentosa in northern Sweden2016Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, nr 12Artikel i tidskrift (Refereegranskat)
  • 18.
    Gustavsson, Simon T.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Enz, Tim J.
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Ophthalmology, University of Basel, Basel, Switzerland.
    Tribble, James R.
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, Mattias
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Lindqvist, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Linden, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Hagström, Anna
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Rutigliani, Carola
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Lardner, Emma
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Stålhammar, Gustav
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
    Williams, Pete A.
    Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Eugeniavägen 12, Solna, Sweden.
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Department of Ophthalmology, University of Iceland, Iceland.
    Nicotinamide prevents retinal vascular dropout in a rat model of ocular hypertension and supports ocular blood supply in glaucoma patients2023Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 64, artikel-id 34Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. To investigate whether nicotinamide (NAM) modulates retinal vasculature in glaucoma.

    METHODS. This was a prospective controlled clinical trial investigating animal and human histopathology. Participants included normotensive and ocular hypertensive rats, postmortem human ocular tissue, glaucoma patients (n = 90), and healthy controls (n = 30). The study utilized histopathology, computer-assisted retinal vasculature analysis, optical coherence tomography angiography (OCTA), and NAM treatment. The main outcome measures included retinal vascular parameters in rats as assessed by AngioTool; retinal vasculature integrity in rats and humans as assessed by histopathology, antibody-staining, and ImageJ-based measurements; and retinal perfusion density (PD) and flux index in humans as assessed by OCTA.

    RESULTS. A number of vessel parameters were altered in ocular hypertension/glaucoma compared to healthy controls. NAM treatment improved the retinal vasculature in ocular hypertensive rats, with an increase in mean vessel area, percentage area covered by vessels, total vessel length, total junctions, and junction density as assessed by AngioTool (all P < 0.05); vessel wall integrity as assessed by VE-cadherin antibody staining was also improved (P < 0.01). In humans, as assessed by OCTA, increases in PD in the optic nerve head and macula complete image (0.7%, P = 0.04 and 1.0%, P = 0.002, respectively) in healthy controls, and an increase in the temporal quadrant of the macula (0.7%, P = 0.02) in glaucoma patients was seen after NAM treatment.

    CONCLUSIONS. NAM can prevent retinal vascular damage in an animal model of glaucoma. After NAM treatment, glaucoma patients and healthy controls demonstrated a small increase in retinal vessel parameters as assessed by OCTA.

    Ladda ner fulltext (pdf)
    fulltext
  • 19.
    Haargaard, Birgitte
    et al.
    Department of Epidemiology Research, Statens Serum Institut, Denmark & Department of Ophthalmology, Glostrup University Hospital, Copenhagen, Denmark.
    Andersen, Elisabeth W
    Department of Epidemiology Research, Statens Serum Institut, Denmark.
    Oudin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin. Department of Epidemiology Research, Statens Serum Institut, Denmark.
    Poulsen, Gry
    Department of Epidemiology Research, Statens Serum Institut, Denmark.
    Wohlfahrt, Jan
    Department of Epidemiology Research, Statens Serum Institut, Denmark.
    la Cour, Morten
    Department of Ophthalmology, Glostrup University Hospital, Copenhagen, Denmark .
    Melbye, Mads
    Department of Epidemiology Research, Statens Serum Institut, Denmark.
    Risk of retinal detachment after pediatric cataract surgery2014Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 55, nr 5, s. 2947-2951Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To determine the long-term risk of retinal detachment following pediatric cataract surgery and to identify risk factors for retinal detachment.

    METHODS: We included all children (aged 0 to 17 years) who during the time period of 1977 to 2005 underwent pediatric cataract surgery in Denmark, excluding cataract cases caused by trauma, or acquired systemic or acquired ocular pathology, and cases with ocular anomalies associated with the development of retinal detachment. Cases of cataract were ascertained from the mandatory Danish National Patient Register, and information on retinal detachment was based on medical chart review.

    RESULTS: Among 1043 eyes of 656 children undergoing surgery for pediatric cataract, 25 eyes (23 children) developed retinal detachment at a median time of 9.1 years after surgery. The overall 20-year risk of retinal detachment was 7% (95% confidence interval [CI]: 3%-11%) among cataract patients. In otherwise normal children having isolated cataract, the risk was 3% (95% CI: 0%-7%). A significantly higher risk of developing retinal detachment was found in children with mental retardation (23% [95% CI: 9%-35%]) or in cataract cases with other ocular or systemic anomalies (16% [95% CI: 6%-24%]).

    CONCLUSIONS: The estimated overall risk of retinal detachment 20 years after pediatric cataract surgery was 7%, but only 3% for isolated cataract. Particularly high risks of retinal detachment after cataract surgery were associated with mental retardation and having other ocular or systemic diseases.

  • 20.
    Harandi, Vahid M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Gaied, Aida RN
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Liu, Jing-Xia
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Unchanged neurotrophic factors and their receptors correlate with sparing in extraocular muscles in amyotrophic lateral sclerosis2016Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, nr 15, s. 6831-6842Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To investigate the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscles (EOMs) by examining the distribution of neurotrophic factors (NTFs) and their receptors in EOMs and limb muscles from ALS transgenic mice.

    Methods: Muscle samples collected from transgenic mice overexpressing human superoxide dismutase type 1 mutations (SOD1G93A, the most widely used mouse model of ALS) at 50 and 150 days as well as age-matched controls were analyzed with immunohistochemistry using antibodies against brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4), glial cell line-derived neurotrophic factor (GDNF), and the neurotrophin receptors p75NTR, tyrosine kinase (Trk) receptor TrkB and TrkC, and GDNF family receptor alpha-1 (GFRα-1).

    Results: There was an intrinsic difference in NTF expression between EOMs and limb muscles in control mice: EOMs presented significantly lower number of neuromuscular junctions (NMJs) labeled for BDNF and NT-4 at 50 days, and for BDNF and GDNF at 150 days, compared with the control limb muscles of corresponding age. In ALS transgenic mice at 150 days, NTF expression in limb muscles was significantly changed but not in EOMs: the limb muscles presented a significant decline in the number of NMJs labeled for BDNF, NT-4, GDNF, p75NTR, TrkB, and TrkC, which was not observed in EOMs.

    Conclusions: The significant differences in expression of NTFs on NMJs between EOMs and limb muscles in both control and ALS transgenic mice suggest that NTF may be involved in the pathogenesis of ALS and the resistance of EOMs to the disease.

    Ladda ner fulltext (pdf)
    fulltext
  • 21.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Stoverud, Karen-Helene
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Author Response: Posture-Dependent Collapse of the Optic Nerve Subarachnoid Space: A Combined MRI and Modeling Study2021Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 62, nr 15, artikel-id 15Artikel i tidskrift (Övrigt vetenskapligt)
    Ladda ner fulltext (pdf)
    fulltext
  • 22.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Stoverud, Karen-Helene
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Posture-dependent collapse of the optic nerve subarachnoid space: A combined MRI and modeling study2021Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 62, nr 4, artikel-id 26Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: We hypothesize that a collapse of the optic nerve subarachnoid space (ONSAS) in the upright posture may protect the eyes from large translamina cribrosa pressure differences (TLCPD) believed to play a role in various optic nerve diseases (e.g., glaucoma). In this study, we combined magnetic resonance imaging (MRI) and mathematical modeling to investigate this potential ONSAS collapse and its effects on the TLCPD.

    METHODS: First, we performed MRI on six healthy volunteers in 6° head-down tilt (HDT) and 13° head-up tilt (HUT) to assess changes in ONSAS volume (measured from the eye to the optic canal) with changes in posture. The volume change reflects optic nerve sheath (ONS) distensibility. Second, we used the MRI data and mathematical modeling to simulate ONSAS pressure and the potential ONSAS collapse in a 90° upright posture.

    RESULTS: The MRI showed a 33% decrease in ONSAS volume from the HDT to HUT (P < 0.001). In the upright posture, the simulations predicted an ONSAS collapse 25 mm behind lamina cribrosa, disrupting the pressure communication between the ONSAS and the intracranial subarachnoid space. The collapse reduced the simulated postural increase in TLCPD by roughly 1 mm Hg, although this reduction was highly sensitive to ONS distensibility, varying between 0 and 4.8 mm Hg when varying the distensibility by ± 1 SD.

    CONCLUSIONS: The ONSAS volume along the optic nerve is posture dependent. The simulations supported the hypothesized ONSAS collapse in the upright posture and showed that even small changes in ONS stiffness/distensibility may affect the TLCPD.

    Ladda ner fulltext (pdf)
    fulltext
  • 23. Holmström, Gerd
    et al.
    Granse, Lotta
    Hellström, Ann
    Larsson, Eva
    Saric, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Sunnqvist, Birgitta
    Törnqvist, Kristina
    Wallin, Agneta
    Ten years of ROP-screening and treatment in Sweden - consideration of modified screening guidelines based on a national quality register2019Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 60, nr 9Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Purpose : Description of ten years of national ROP-screening and treatment in Sweden and evaluation of the national screening program for ROP.

    Methods : The study is based on a national register for ROP, SWEDROP, with around 96% coverage. According to Swedish guidelines, all infants born at 30 weeks gestational age (GA) or less, as well as children born later but being extremely sick, should be screened for ROP during the neonatal period. Birth data are validated in the Swedish neonatal quality register, SNQ.

    Results : During the ten-year period between 2008 and 2017, 7257 infants with a GA of 30 weeks or less were registered in SWEDROP and 46.294 examinations were performed, of which 5.328 (11.5%) in infants born in gestational week 30. Mean GA was 27.6 w (range 21-30 w) and mean BW was 1116 g (range 390-2405 g). Overall, during the ten years, ROP was found in 31.8% (range 26.8-36.8%) and treatment for ROP was performed in 6% (range 4.1-7.7%) of the screened infants. Only nine infants with GA 28 w and four with GA 29 w were treated for ROP. No infant with GA 30 w was treated. Eighty-two per cent (361/441) of the treated infants had laser only and 17.7% (78/441) were treated with Anti-VEGF, alone (17 infants) or in combination with laser and/or other treatment.

    Conclusions : SWEDROP is a national register for ROP with a high national coverage. The incidence of ROP and frequency of treatment remained similar over the ten-year period. Only 13 infants born at 28 – 29 weeks GA and no child born at 30 w GA were treated for ROP. Modification of guidelines is considered, with lowering the upper limit of screening with one week, i.e. to less than 30 weeks GA. During the ten-year study period, this would have resulted in a reduction of 1680 infants (23.2%) screened for ROP and of 5.328 (11.5%) examinations.

  • 24. Huang, Xiu-Feng
    et al.
    Li, Zhixiu
    De Guzman, Erika
    Robinson, Philip
    Gensler, Lianne
    Ward, Michael M.
    Rahbar, Mohammad Hossein
    Lee, MinJae
    Weisman, Michael H.
    Macfarlane, Gary J.
    Jones, Gareth T.
    Klingberg, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    McCluskey, Peter
    Wakefield, Denis
    Coombes, Jeff S.
    Singh, Maria A. Fiatarone
    Mavros, Yorgi
    Vlahovich, Nicole
    Hughes, David C.
    Marzo-Ortega, Helena
    Van der Horste-Bruinsma, Irene
    O'Shea, Finbar
    Martin, Tammy M.
    Rosenbaum, James
    Breban, Maxime
    Jin, Zi-Bing
    Leo, Paul
    Reveille, John D.
    Wordsworth, B. Paul
    Brown, Matthew A.
    Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci2020Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 61, nr 6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B 27 , implying a shared etiology. This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS.

    METHODS. We undertook the GWAS analyses in 2752 patients with AS with AAU (cases) and 3836 patients with AS without AAU (controls). There were 7,436,415 single-nucleotide polymorphisms (SNPs) available alter SNP microarray genotyping, imputation, and quality-control filtering.

    RESULTS. We identified one locus associated with AAU at genomewide significance: rs9378248 (P = 2.69 x 10(-8), odds ratio [OR] = 0.78), lying close to HLA-B. Suggestive association was observed at 11 additional loci, including previously reported AS loci ERAP1 (rs27529, P = 2.19 x 10(-7), OR = 1.22) and NOS2 (rs2274894, P = 8.22 x 10(-7), OR = 0.83). Multiple novel suggestive associations were also identified, including MERTK (rsl0171979, P = 2.56 x 10(-6), OR = 1.20), KIFAP3 (rs508063, P = 5.64 x 10(-7), OR = 1.20), CLCN7 (rs67412457, P = 1.33 x 10(-6), OR = 1.25), ACAA2 (rs9947182, P = 9.70 x 10(-7), OR = 1.37), and 5 intergenic loci. The SNP-based heritability is approximately 0.5 for AS alone, and is much higher (approximately 0.7) for AS with AAU. Consistent with the high heritability, a genomewide polygenic risk score shows strong power in identifying individuals at high risk of either AS with AAU or AS alone.

    CONCLUSIONS. We report here the first GWAS for AAU and identify new susceptibility loci. Our findings confirm the strong overlap in etiopathogenesis of AAU with AS, and also provide new insights into the genetic basis of AAU.

  • 25.
    Janbaz, Adrihan H.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Lindström, Mona
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Liu, Jingxia
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Intermediate Filaments in the Human Extraocular Muscles2014Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 55, nr 8, s. 5151-5159Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE.

    To investigate the distribution of the intermediate filament (IF) proteins desmin, vimentin, and nestin in human extraocular muscles (EOMs). METHODS. Healthy adult EOM samples were serially sectioned (5 and 1 mu m) and processed for immunohistochemistry, with specific antibodies (Abs) against desmin, vimentin, and nestin and different myosin heavy chains (MyHCs), including the newly characterized Ab MYH7b against MyHC slow tonic. The distribution of desmin was also studied in EOMs at 16 to 18 weeks of gestation.

    RESULTS.

    Desmin was present in the vast majority of muscle fibers. Notably, muscle fibers that contained MyHC slow tonic were either unlabeled or very weakly labeled with three different Abs against desmin. These muscle fibers had normal cytoarchitecture and intact basement membrane. In fetal muscle, desmin was also absent or weak in myotubes containing MyHC slow tonic. Nestin was detected in a large proportion of muscle fibers in the orbital layer and to some extent also in the global layer, whereas no muscle fibers contained vimentin. Desmin and nestin were enriched at neuromuscular junctions, as in limb muscle. In contrast, some myotendinous junctions lacked desmin or nestin.

    CONCLUSIONS.

    The human EOMs differed significantly from the other muscles in the body with respect to their IF composition. Desmin, hitherto regarded as a ubiquitous muscle cytoskeletal protein, was absent or only present in trace amounts in a subset of normal muscle fibers in adult and fetal EOMs. Nestin, normally downregulated early in the postnatal period, was present in a high proportion of adult muscle fibers.

  • 26.
    Johannesson, Gauti
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Hallberg, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Ambarki, Khalid
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Eklund, Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Linden, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Age-dependency of ocular parameters - a cross sectional study of young and old healthy subjects2015Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, nr 7, artikel-id Meeting Abstract: 116Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Purpose: To investigate aging effect on ocular parameters inkluding intraocular pressure (IOP) measured with different tonometry methods in healthy young (HY) and elderly (HE) subjects.

    Methods: Fifty eyes of 50 HY subjects (28 females, 22-31 years of age) and 43 eyes of 43 HE subjects (22 females, 64-79 years of age) were included. IOP was measured with four tonometry methods in a standardized order: Ocular Response Analyser (ORA), Dynamic Contour Tonometry (DCT), Applanation Resonance Tonometry (ART) and Goldmann Applanation Tonometry (GAT). Other measurements included axial length (AL), central corneal thickness (CCT), corneal curvature (CC), ocular pulse amplitude (OPA) and aqueous humor (aq).

    Results: The mean IOP (HY/HE; mmHg ± standard deviation) was 13.9 ± 2.7/16.4 ± 3.4 with ORA, 15.1 ± 2.1/16.3 ± 3.1 with DCT, 12.3 ± 2.0/13.7 ± 2.8 with GAT and 13.1 ± 2.2/12.1 ± 2.5 with ART. IOP was significantly higher (difference ± standard error) in HE compared to HY measured with ORA (+2.5 mmHg ± 0.6), GAT (+1.4 ± 0.5) and DCT (+1.2 ± 0.6). There was a trend towards lower IOP in HE when measured with ART (-1.0 ± 0.5, p=0.05). There was no difference between HE and HY in CCT, CC, AL or OPA.

    Conclusions: Tonometry methods are affected differently by age. IOP was measured higher in elderly people with ORA, DCT and GAT in this Scandinavian population. This effect was not seen in measurements with ART. Other ocular parameters did not differ between the age groups indicating that these measured parameters are not influenced by age in this population.

  • 27.
    Jóhannesson, Gauti
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hallberg, Per
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Lindén, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Intraocular Pressure Decrease Does Not Affect Blood Flow Rate of Ophthalmic Artery in Ocular Hypertension2020Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 61, nr 12, artikel-id 17Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To investigate if decrease of IOP affects the volumetric blood flow rate in the ophthalmic artery (OA) in patients with previously untreated ocular hypertension.

    METHODS: Subjects with untreated ocular hypertension (n = 30; mean age 67 +/- 8 years; 14 females) underwent ophthalmologic examination and a 3-Tesla magnetic resonance imaging investigation. The magnetic resonance imaging included three-dimensional high-resolution phase-contrast magnetic resonance imaging to measure the OA blood flow rate. The subjects received latanoprost once daily in the eye with higher pressure, the untreated eye served as control. The same measurements were repeated approximately 1 week later.

    RESULTS: The mean OA blood flow rate before and after treatment was 12.4 +/- 4.4 and 12.4 +/- 4.6 mL/min in the treated eye (mean +/- SD; P = 0.92) and 13.5 +/- 5.2 and 13.4 +/- 4.1 mL/min in the control eye (P = 0.92). There was no significant difference between the treated and control eye regarding blood flow rate before (P = 0.13) or after treatment (P = 0.18), or change in blood flow rate after treatment (0.1 +/- 3.1 vs.-0.1 +/- 4.0 mL/min, P = 0.84). Latanoprost decreased the IOP by 7.2 +/- 3.1 mm Hg in the treated eye (P < 0.01).

    CONCLUSIONS: The results indicate that a significant lowering of IOP does not affect the blood flow rate of the OA in ocular hypertension subjects. The ability to maintain blood supply to the eye independent of the IOP could be a protective mechanism in preserving vision in subjects with ocular hypertension.

    Ladda ner fulltext (pdf)
    fulltext
  • 28.
    Kahsay, Abraha
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Dennhag, Nils
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Liu, Jing-Xia
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Nord, Hanna
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Rönnbäck, Hugo
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Thorell, Anna Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    von Hofsten, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Domellöf, Fatima Pedrosa
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Obscurin maintains myofiber identity in extraocular muscles2024Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 65, nr 2, artikel-id 19Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The cytoskeleton of the extraocular muscles (EOMs) is significantly different from that of other muscles. We aimed to investigate the role of obscurin, a fundamental cytoskeletal protein, in the EOMs.

    Methods: The distribution of obscurin in human and zebrafish EOMs was compared using immunohistochemistry. The two obscurin genes in zebrafish, obscna and obscnb, were knocked out using CRISPR/Cas9, and the EOMs were investigated using immunohistochemistry, qPCR, and in situ hybridization. The optokinetic reflex (OKR) in five-day-old larvae and adult obscna−/−;obscnb−/− and sibling control zebrafish was analyzed. Swimming distance was recorded at the same age.

    Results: The obscurin distribution pattern was similar in human and zebrafish EOMs. The proportion of slow and fast myofibers was reduced in obscna−/−;obscnb−/− zebrafish EOMs but not in trunk muscle, whereas the number of myofibers containing cardiac myosin myh7 was significantly increased in EOMs of obscurin double mutants. Loss of obscurin resulted in less OKRs in zebrafish larvae but not in adult zebrafish.

    Conclusions: Obscurin expression is conserved in normal human and zebrafish EOMs. Loss of obscurin induces a myofiber type shift in the EOMs, with upregulation of cardiac myosin heavy chain, myh7, showing an adaptation strategy in EOMs. Our model will facilitate further studies in conditions related to obscurin.

    Ladda ner fulltext (pdf)
    fulltext
  • 29.
    Kawasaki, Aki
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Crippa, Sylvain V
    Kardon, Randy
    Leon, Lorette
    Hamel, Christian
    Characterization of pupil responses to blue and red light stimuli in autosomal dominant retinitis pigmentosa due to NR2E3 mutation2012Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 53, nr 9, s. 5562-5569Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose. We characterized the pupil responses that reflect rod, cone, and melanopsin function in a genetically homogeneous cohort of patients with autosomal dominant retinitis pigmentosa (adRP).

    Methods. Nine patients with Gly56Arg mutation of the NR2E3 gene and 12 control subjects were studied. Pupil and subjective visual responses to red and blue light flashes over a 7 log-unit range of intensities were recorded under dark and light adaptation. The pupil responses were plotted against stimulus intensity to obtain red-light and blue-light response curves.

    Results. In the dark-adapted blue-light stimulus condition, patients showed significantly higher threshold intensities for visual perception and for a pupil response compared to controls (P = 0.02 and P = 0.006, respectively). The rod-dependent, blue-light pupil responses decreased with disease progression. In contrast, the cone-dependent pupil responses (light-adapted red-light stimulus condition) did not differ between patients and controls. The difference in the retinal sensitivity to blue and red stimuli was the most sensitive parameter to detect photoreceptor dysfunction. Unexpectedly, the melanopsin-mediated pupil response was decreased in patients (P = 0.02).

    Conclusions. Pupil responses of patients with NR2E3-associated adRP demonstrated reduced retinal sensitivity to dim blue light under dark adaptation, presumably reflecting decreased rod function. Rod-dependent pupil responses were quantifiable in all patients, including those with non-recordable scotopic electroretinogram, and correlated with the extent of clinical disease. Thus, the chromatic pupil light reflex can be used to monitor photoreceptor degeneration over a larger range of disease progression compared to standard electrophysiology.

  • 30.
    Kjellgren, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Ryan, Michelle
    Ohlendieck, Kay
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Sarco(endo)plasmic reticulum ca2+ATPases (SERCA1 and 2) in human extraocular muscles2003Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, nr 12, s. 5057-5062Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To investigate the composition of the fibers in human extraocular muscles (EOMs) with respect to the sarco(endo)plasmic reticulum Ca(2+)ATPases (SERCA)-1 and -2 and to investigate possible correlations between SERCA and myosin heavy chain (MyHC) composition. METHODS: EOM samples were processed for immunocytochemistry with monoclonal antibodies specific against SERCA1 (fast isoform), SERCA2 (slow isoform), or different MyHCs. A total of 1571 fibers were analyzed. Microsomal EOM fractions were analyzed with SDS-PAGE and immunoblots. RESULTS: The fast fibers, containing MyHCIIa, accounted for 79% of the fibers in the orbital layer (OL) and 74% in the global layer (GL). More than 99% of these fibers contained SERCA1, and 86% of them coexpressed SERCA1 and -2. Almost all slow fibers stained with SERCA2; 54% of those in the GL and all in the OL coexpressed SERCA1 and -2. Fifteen percent of the fibers in the GL and less than 1% in the OL were MyHCeom(pos)/MyHCIIa(neg) fibers. All these contained SERCA1 and in the OL also stained strongly with anti-SERCA2. Biochemically SERCA2 was more abundant than SERCA1. CONCLUSIONS: The human EOMs had a very complex pattern of expression of the major protein regulating fiber relaxation rate. The coexistence of SERCA1 and -2, together with complex mixtures of MyHCs in most of the fibers provide the human EOMs with a unique molecular portfolio that allows a highly specific fine-tuning regimen of contraction and relaxation.

  • 31.
    Kjellgren, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Stål, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Larsson, Lars
    Uppsala University.
    Fürst, Dieter
    University of Bonn.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Uncoordinated expression of myosin heavy chains and myosin-binding protein C isoforms in human extraocular muscles2006Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 47, nr 10, s. 4188-4193Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To examine the distribution of myosin-binding protein C (MyBP-C) in human extraocular muscles (EOMs) and to correlate the myosin heavy chain (MyHC) and the MyBP-C composition of the fibers. METHODS: Samples from 17 EOMs, 3 levator palpebrae (LP), and 6 limb muscles were analyzed with SDS-PAGE and immunoblot or processed for immunocytochemistry with monoclonal antibodies (mAbs) against MyBP-C-fast, MyBP-C-slow, MyHCIIa, MyHCI, MyHCsto, MyHCalpha-cardiac, and MyHCemb. RESULTS: In the limb muscle samples, fast fibers were labeled with anti-MyBP-C-fast and anti-MyBP-C-slow, whereas the slow fibers were immunostained with anti-MyBP-C-slow only, in accordance with previous studies. In 11 EOM samples MyBP-C-fast was not detected, and weak staining with anti-MyBP-C-fast was seen only in a few fibers in the proximal part of 2 muscles. The mAb against MyBP-C-slow labeled all fibers, but fibers containing MyHCI were generally more strongly stained. In the levator palpebrae, immunostaining with anti-MyBP-C-fast was present in some fibers labeled with anti-MyHCIIa and/or anti-MyHCeom. MyBP-C-fast and -intermediate were not detected biochemically in the EOMs. CONCLUSIONS: The lack of MyBP-C-fast and intermediate is an additional feature of the human EOM allotype. The true EOMs have a unique myofibrillar protein isoform composition reflecting their special structural and functional properties. The levator palpebrae muscle phenotype is intermediate between that of the EOMs and the limb muscles.

  • 32.
    Kjellgren, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Andersen, Jesper
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Myosin heavy chain isoforms in human extraocular muscle2003Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, nr 4, s. 1419-1425Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To investigate the myosin heavy chain (MyHC) composition of human extraocular (EOM) and levator palpebrae (LP) muscle fibers. METHODS: Adult human EOMs and LP were studied with SDS-PAGE, immunoblots, and immunocytochemistry, with antibodies against six MyHC isoforms. Myofibrillar adenosine triphosphatase (mATPase) and reduced nicotinamide adenine dinucleotide (NADH)-TR activity and fiber area were also determined. RESULTS: Most of the fibers in both layers stained strongly with anti-MyHCIIa. Approximately 14% of the fibers in the global layer and 16% in the orbital layer were labeled with anti-MyHCI. The remaining 24% of the fibers in the global layer and 3% in the orbital layer were not stained with either of these two antibodies, but were reactive to anti-MyHCeom (MyHCeom(pos)/MyHCIIa(neg) fibers). The fibers stained with anti-MyHCI had acid-stable mATPase activity, and the remainder of the fibers had alkaline-stable mATPase activity. Almost all the slow fibers stained with both anti-MyHCI and anti-MyHCslow tonic in both layers. Anti-MyHCalpha-cardiac stained approximately 26% of these slow fibers in the orbital layer and 7% in the global layer. Some slow fibers in both layers lacked staining with anti-MyHCslow tonic or with anti-MyHCalpha-cardiac. MyHCemb and/or MyHCeom were also present in some of the fibers of all the groups. The LP did not stain with anti-MyHCslow tonic. CONCLUSIONS: The present study revealed that the human EOMs have a very complex fiber type and MyHC composition and differ significantly from the EOMs of other species. The features of the LP were distinct from those of the four recti, the obliquus superior, and the limb muscles.

  • 33.
    Kjellgren, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Virtanen, Ismo
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Laminin isoforms in human extraocular muscles2004Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 45, nr 12, s. 4233-4239Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To determine the laminin isoform composition of the basement membranes (BMs) in the human extraocular muscles (EOMs) and relate it to the fact that EOMs are spared in laminin alpha2-chain-deficient congenital muscular dystrophy. METHODS: Samples from adult human EOMs and limb muscle were processed for immunocytochemistry, with monoclonal antibodies against laminin chains (Ln) alpha1 to -5, beta1 and -2, and gamma1. Neuromuscular junctions (NMJs) were identified with acetylcholinesterase reaction. The capillary density was measured in sections stained with anti-Lnalpha5. RESULTS: The extrasynaptic BM of the EOM muscle fibers contained Lnalpha2, -beta1, -beta2, and -gamma1, and, in contrast to limb muscle, it also contained Lnalpha4 and -alpha5, to some extent. The distinct laminin composition of the EOMs was confirmed by the presence of Lutheran protein, an alpha5-chain-specific receptor not found in limb muscle. At the NMJs, there was increased expression of Lnalpha4 and expression of Lnalpha2, -alpha5, -beta1, -beta2, and -gamma1 was also maintained. The capillary density was very high (1050 +/- 190 capillaries/mm(2)) in the EOMs and significantly (P < 0.05) higher in the orbital (1170 +/- 180 capillaries/mm(2)) than in the global (930 +/- 110 capillaries/mm(2)) layer. CONCLUSIONS: The human EOMs showed important differences in laminin isoform composition and capillary density when compared with human limb muscle and muscles of other species. The presence of additional laminin isoforms other than laminin-2 in the BM of the extrasynaptic sarcolemma could partly explain the sparing of the EOMs in Lnalpha2-deficient congenital muscular dystrophy.

  • 34.
    Kristiansen, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Holmlund, Petter
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Linden, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Department of Ophthalmology, University of Iceland, Reykjavik, Iceland.
    Optic nerve subarachnoid space posture dependency: an MRI study in subjects with normal tension glaucoma and healthy controls2023Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 64, nr 15, artikel-id 20Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The purpose of this study was to examine the differences of optic nerve subarachnoid space (ONSAS) volume in patients with normal tension glaucoma (NTG) and healthy controls in different body positions.

    Methods: Eight patients with NTG and seven healthy controls underwent magnetic resonance imaging (MRI) examinations in head up tilt (HUT) +11 degrees and head down tilt (HDT) -5 degrees positions according to a randomized protocol determining the starting position. The ONSAS volume in both body positions was measured and compared between the two groups. The results were analyzed using a generalized linear model.

    Results: Between HDT and HUT, the postural ONSAS volume change was dependent on starting position (P < 0.001) and group (P = 0.003, NTG versus healthy). A subgroup analysis of those that were randomized to HUT examination first, coming directly from an upright position, showed that the patients with NTG had significantly larger positional ONSAS volume changes compared to the healthy controls; 121 ± 22 µL vs. 65 ± 37 µL (P = 0.049). Analysis of the ONSAS volume distribution showed different profiles for patients with NTG and healthy controls.

    Conclusions: There was a significant difference in ONSAS volume change between patients with NTG and healthy subjects when subjected to posture changes, specifically when going from upright to head-down posture. This indicates that patients with NTG had been exposed to a lower ONSAS pressure when they came from the upright posture, which suggests an increased translaminar pressure difference in upright position. This may support the theory that NTG has a dysfunction in an occlusion mechanism of the optic nerve sheath that could cause abnormally negative ONSAS pressures in upright posture.

    Ladda ner fulltext (pdf)
    fulltext
  • 35.
    Kristiansen, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Linden, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hallberg, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Blood flow rate of ophthalmic artery in patients with normal tension glaucoma and healthy controls2018Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, nr 9Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Purpose: To determine the blood flow rate of the ophthalmic artery (OA) in patients with Normal Tension Glaucoma (NTG) compared to age-matched healthy controls using phase-contrast magnetic resonance imaging (PCMRI).

    Methods: Seventeen patients with treated NTG (11 female; mean age: 70±9 years) and 16 age-matched healthy controls (10 female; mean age: 71±9 years) underwent PCMRI using a 3-Tesla scanner as well as ophthalmological examinations including visual acuity, Goldmann Applanation Tonometry, Humphrey perimetry and fundoscopy. Ophthalmic blood flow was acquired using a 2D PCMRI sequence set to a spatial resolution of 0.35mm/pixel. Mean flow rate and cross-sectional area was calculated using Segment Software. The eye with the most severe glaucomatous damage classified by visual field index (VFI) was chosen for comparison. The primary outcome was blood flow rate of OA.

    Results: The mean VFI was 41% ± 26 (mean±SD) for the worse NTG eyes. The intraocular pressure was 13.6±2.6 mmHg for NTG eyes and 13.8±2.1 mmHg for control eyes. The blood flow rate in the NTG group was 9.6±3.7 ml/min compared to 11.8±5.5 ml/min in the control group. The area was 1.7±0.3 mm2 and 2.0±0.6 mm2 respectively. No statistical significance was found between NTG and the control group regarding blood flow rate (p=0.07) or OA area (p=0.12).

    Conclusions: Despite OA being an anastomosis between the intracranial and extracranial circulation, possibly generating an eye unrelated variability in blood flow, we found a trend level reduction of approximately 2 ml/min in NTG. The finding warrants blood flow rate analysis of smaller arteries specifically supplying the eye, e.g. the central retinal artery.

  • 36.
    Köhn, Linda
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Burstedt, Marie SI
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Jonsson, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Kadzhaev, Konstantin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Haamer, Eneli
    Asper Biotech, Tartu, Estonia.
    Sandgren, Ola
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Golovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Carrier of R14W in carbonic anhydrase IV presents Bothnia dystrophy phenotype caused by two allelic mutations in RLBP12008Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 49, nr 7, s. 3172-3177Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Bothnia dystrophy (BD) is an autosomal recessive retinitis pigmentosa (arRP) associated with the c.700C>T mutation in the RLBP1 gene. Testing of patients with BD has revealed the c.700C>T mutation on one or both alleles. The purpose of this study was to elucidate the underlying genetic mechanisms along with a clinical evaluation of the heterozygous patients with BD.

    Methods: Patients with BD heterozygous for the RLBP1 c.700C>T were tested for 848 mutations by arrayed primer-extension technology. Further mutation detection was performed by PCR-restriction fragment length polymorphism (RFLP), sequencing, denaturing (d)HLPC and allelic discrimination. The ophthalmic examinations were performed in all c.700C>T heterozygotes.

    Results: The clinical findings in 10 BD heterozygotes were similar to those in the homozygotes. The presence of a second mutation, c.677T>A, corresponding to p.M226K was detected in all 10 cases. Segregation analysis showed that the mutations were allelic, and the patients were compound heterozygotes [c.677T>A]+[c.700C>T]. One of those patients was also a carrier of the c.40C>T corresponding to the p.R14W change in carbonic anhydrase IV (CAIV) associated with autosomal dominant RP, RP17. His mother, a carrier of the identical change was declared healthy after ophthalmic examination. This sequence variant was found in 6 of 143 tested blood donors.

    Conclusions: The high frequency of arRP in northern Sweden is due to two mutations in the RLBP1 gene: c.677T>A and c.700C>T. BD is caused by the loss of CRALBP function due to changed physical features and impaired activity of retinoid binding. The CAIV p.R14W sequence variant found in one of the patients with a BD phenotype is a benign polymorphism in a population of northern Sweden.

  • 37. Lagali, Neil S.
    et al.
    Allgeier, Stephan
    Guimaraes, Pedro
    Badian, Reza A.
    Ruggeri, Alfredo
    Koehler, Bernd
    Utheim, Tor Paaske
    Peebo, Beatrice Bourghardt
    Peterson, Magnus
    Dahlin, Lars
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Analysis of corneal subbasal nerve plexus from wide-area mosaics in healthy subjects and in type 2 diabetics2016Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, nr 12Artikel i tidskrift (Refereegranskat)
  • 38. Lagali, Neil S.
    et al.
    Allgeier, Stephan
    Guimaraes, Pedro
    Badian, Reza A.
    Ruggeri, Alfredo
    Koehler, Bernd
    Utheim, Tor Paaske
    Peebo, Beatrice
    Peterson, Magnus
    Dahlin, Lars B.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Reduced Corneal Nerve Fiber Density in Type 2 Diabetes by Wide-Area Mosaic Analysis2017Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 58, nr 14, s. 6318-6327Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. To determine if corneal subbasal nerve plexus (SBP) parameters derived from wide-area depth-corrected mosaic images are associated with type 2 diabetes.

    METHODS. One hundred sixty-three mosaics were produced from eyes of 82 subjects by laser-scanning in vivo confocal microscopy (IVCM). Subjects were of the same age, without (43 subjects) or with type 2 diabetes (39 subjects). Mosaic corneal nerve fiber length density (mCNFL) and apical whorl corneal nerve fiber length density (wCNFL) were quantified and related to the presence and duration of diabetes (short duration < 10 years and long duration ≥10 years).

    RESULTS. In mosaics with a mean size of 6 mm2 in subjects aged 69.1 ± 1.2 years, mCNFL in type 2 diabetes was reduced relative to nondiabetic subjects (13.1 ± 4.2 vs. 15.0 ± 3.2 mm/mm2, P = 0.018). Also reduced relative to nondiabetic subjects was mCNFL in both short-duration (14.0 ± 4.0 mm/mm2, 3.2 ± 3.9 years since diagnosis) and long-duration diabetes (12.7 ± 4.2 mm/mm2, 15.4 ± 4.2 years since diagnosis; ANOVA P =0.023). Lower mCNFL was associated with presence of diabetes (=0.032) and increased hemoglobin A1c (HbA1c) levels (P = 0.047). By contrast, wCNFL was unaffected by diabetes or HbA1c (P > 0.05). Global SBP patterns revealed marked degeneration of secondary nerve fiber branches outside the whorl region in long-duration diabetes.

    CONCLUSIONS. Wide-area mosaic images provide reference values for mCNFL and wCNFL and reveal a progressive degeneration of the SBP with increasing duration of type 2 diabetes.

    Ladda ner fulltext (pdf)
    fulltext
  • 39.
    Lindström, Mona
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Tjust, Anton E.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Domellöf, Fatima Pedrosa
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Pax7-Positive Cells/Satellite Cells in Human Extraocular Muscles2015Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, nr 10, s. 6132-6143Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. We quantified and investigated the distribution of Pax7-positive cells/satellite cells (SCs) in the human extraocular muscles (EOMs). METHODS. An immunofluorescence multiple-marker method simultaneously combining two SC markers (Pax7, NCAM), detection of the basement membrane (laminin) and cell nuclei (4',6-diamidino-2-phenylindole [DAPI]), was used on the anterior, middle, and posterior portions of EOMs from five healthy donors. Pax7-positive cell and SC content, myonuclear content, myofiber cross-sectional area, and myonuclear domain were analyzed in single cross-sections. Between 3915 and 13,536 myofibers per muscle cross-section and myofibers from the entire EOM cross-section were analyzed for quantification of Pax7-positive cells per myofiber (Pax7/F).

    RESULTS. The number of Pax7/F in the human EOMs varies along the length of the muscle with twice as high Pax7/F in the anterior part of the EOMs, but within the range of what has been previously reported for normal adult limb muscles. Furthermore, there are Pax7-positive cells in positions other than the classical SC position and the myonuclear domain size of adult EOMs is noticeably smaller than that previously reported for other adult skeletal muscles.

    CONCLUSIONS. Previous data on differences in Pax7-positive cell/SC abundance between EOMs and limb muscles must be reconsidered and the characteristics of different Pax7-positive cell populations further investigated. Higher numbers of Pax7-positive cells in the anterior portion of the EOMs may have a bearing for strabismus surgery involving sectioning of the muscle fibers.

  • 40.
    Liu, Jing-Xia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Different impact of ALS on laminin isoforms in human extraocular muscles versus limb muscles2011Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 52, nr 7, s. 4842-4852Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose. To determ ine the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscles (EOMs) by examining the laminin isoform composition of the basement membranes (BMs) in EOMs and limb muscles from donors with ALS.

    Methods. Muscle samples collected at autopsy from ALS donors and from transgenic mice overexpressing human SOD1 mutations (D90A or G93A), and age-matched controls were analyzed with immunohistochemistry using antibodies against laminin chain α2 (Lnα2), Lnα4, Lnα5, Lnβ1, Lnβ2 and Lnγ1. Neuromuscular junctions (NMJs) were identified with α-bungarotoxin.

    Results. Lnα2, the hallmark chain of skeletal muscle, and Lnβ2 were absent or partially absent from the BMs in a variable number of muscle fibers in most of the ALS EOMs. Three ALS donors showed dramatic decrease in the levels of these chains around their muscle fibers and NMJs. Changes in Lnα2 were not age-related and were also present in EOMs of ALS mouse models. Lnα4 was preserved in the majority of NMJs in EOM but absent in the majority of NMJs in limb muscle of ALS. The BMs around muscle fibers, NMJs, nerves and blood vessels of the majority of EOMs of ALS donors had rather normal appearance and laminin composition, but heterogeneity was observed among EOM samples of individual ALS donors and between ALS donors.

    Conclusions. The present study showed distinct impact of ALS on EOMs as compared to limb muscles. The EOMs maintained a normal laminin composition in their NMJs which may be instrumental for the fact that they are not typically affected in ALS.

  • 41.
    Liu, Jing-Xia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Domellöf, Fatima Pedrosa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Complex Correlations Between Desmin Content, Myofiber Types, and Innervation Patterns in the Human Extraocular Muscles2020Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 61, nr 3, artikel-id 15Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. To investigate whether the distribution of intermediate filament protein desmin is related to the different patterns of innervation in the human extraocular muscles (EOMs).

    METHODS. EOM samples were analyzed with immunohistochemistry using antibodies against desmin, vimentin, different myosin heavy chain (MyHC) isoforms, and fetal and adult acetylcholine receptor (AChR) subunits. Neuromuscular junctions (NMJs) were identified with alpha-bungarotoxin or with antibodies against neurofilament and synaptophysin.

    RESULTS. Desmin was present in the vast majority of myofibers, but it was weakly present or absent in a limited area in the close vicinity of the single en plaque NMJs in less than half of these myofibers. Desmin was either present or lacking in MyHCsto/I myofibers displaying multiple en grappe endings but present in MyHCsto/I myofibers receiving spiral nerve endings. In MyHCeom myofibers displaying multiterminal en plaque endings, desmin was either present or absent irrespective of AChR subunits or EOM layer. Vimentin did not substitute for the lack of desmin.

    CONCLUSIONS. The results indicate that the human EOMs have a more complex cytoskeletal organization than other muscles and suggest additional signalling mechanisms from the NMJs to the myofibers.

    Ladda ner fulltext (pdf)
    fulltext
  • 42.
    Liu, Jing-Xia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Domellöf, Fatima Pedrosa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Cytoskeletal Proteins in Myotendinous Junctions of Human Extraocular Muscles2021Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 62, nr 2, s. 1-10Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The purpose of this study was to investigate the cytoskeletal composition of myotendinous junctions (MTJs) in the human extraocular muscles (EOMs). Desmin and other major cytoskeletal proteins are enriched at the MTJs of ordinary myofibers, where they are proposed to be of particular importance for force transmission and required to maintain myofiber integrity. Methods: EOM and limb muscle samples were analyzed with immunohistochemistry using antibodies against the intermediate filament proteins desmin, nestin, keratin 19, vimentin, and different myosin heavy chain (MyHC) isoforms. MTJs were identified by labeling with antibodies against laminin or tenascin. Results: In contrast to MTJs in lumbrical muscle where desmin, nestin, and keratin 19 were always present, approximately one-third of the MTJs in the EOMs lacked either desmin and/or nestin, and all MTJs lacked keratin 19. Approximately 6% of the MTJs in the EOMs lacked all of these key cytoskeletal proteins. Conclusions: The cytoskeletal protein composition of MTJs in human EOMs differed significantly from that of MTJs in limb muscles. These differences in cytoskeletal protein composition may indicate particular adaptation to meet the functional requirements of the EOMs.

    Ladda ner fulltext (pdf)
    fulltext
  • 43.
    Liu, Jing-Xia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    A novel type of multiterminal motor endplate in human extraocular muscles2018Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, nr 1, s. 539-548Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To investigate the relation between type of motor endplate, acetylcholine receptor (AChR) subunit composition, and fiber types in human extraocular muscles (EOMs).

    Methods: EOM samples collected from subjects aged 34 to 82 years were serially sectioned and processed for immunohistochemistry, with specific antibodies against different myosin heavy chain (MyHC) isoforms, neurofilament, synaptophysin, and adult epsilon (ε) and fetal gamma (γ) AChR subunits as well as α-bungarotoxin.

    Results: A novel type of motor endplate consisting of large, multiterminal en plaque endings was found in human EOMs, in addition to the previously well-described single en plaque and multiple en grappe endplates. Such novel endplates were abundant but exclusively observed in myofibers lacking MyHC slow and fast IIa but containing MyHC extraocular (MyHCeom), isoforms. Multiple en grappe endings were found only in myofibers containing MyHC slow-tonic isoform and contained fetal γ AChR subunit. Adult ε and fetal γ AChR subunits, alone or combined, were found in the multiterminal endplates. Distinct AChR subunits were present in adjacent motor endplates of a given myofiber containing MyHCeom.

    Conclusions: Human EOMs have a more complex innervation pattern than previously described, comprising also a novel type of multiterminal motor endplate present in myofibers containing MyHCeom. The heterogeneity in AChR subunit composition in a given myofiber suggests the possible presence of polyneuronal innervation in human EOMs.

    Ladda ner fulltext (pdf)
    fulltext
  • 44.
    Liu, Jing-Xia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Willison, Hugh J
    Pedrosa-Domellof, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Immunolocalisation of GQ1b and related gangliosides in human extraocular neuromuscular junctions and muscle spindles2009Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 50, nr 7, s. 3226-3232Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To examine the distribution of anti-GQ1b, -GT1a and -GD1b antibody binding in human extraocular muscles (EOMs), axial and limb muscles and muscle spindles and thereby test the hypothesis that their distinctive ganglioside composition provides the molecular basis for selective involvement of EOMs and muscle spindles in Miller Fisher syndrome.

    Methods: Muscle samples from adult human EOMs, vastus lateralis, biceps brachii, lumbrical, psoas and deep muscles of the neck were processed for immunohistochemistry, with monoclonal antibodies against ganglioside GQ1b, GT1a and GD1b. Neuromuscular junctions (NMJs) were detected by a-bungarotoxin binding and by acetycholinesterase reaction.

    Results: The vast majority of motor endplates of human EOMs richly bound anti-GQ1b, -GT1a, and -GD1b ganglioside antibodies. Anti-GQ1b, -GT1a, and -GD1b ganglioside antibody bindings to NMJs in human limb and axial muscle were very scarce but the nerve terminals inside muscle spindles and in direct contact with intrafusal fibers were labeled with anti- GQ1b, -GT1a and -GD1b ganglioside antibodies.

    Conclusions: The abundant and synaptic-specific binding of anti-GQ1b, -GT1a, and -GD1b ganglioside antibodies and the rich capillary supply in the human EOMs may partly explain the selective paralysis of these muscles in Miller Fisher syndrome.

  • 45.
    Lundberg, Björn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Behndig, Anders B
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    The mydriatic effect of intracameral epinine hydrochloride2009Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 50, nr 11, s. 5336-5338Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. To compare the mydriatic effect and the short-term corneal endothelial safety of intracamerally injected N-methyl-3,4-dihydroxyphenylamine (epinine) to phenylephrine in a porcine eye model.

    METHODS. One hundred and twelve eyes from newly slaughtered pigs were used in this study. After pretreatment with 20 mg of intracameral acetylcholine to give miosis, 0.15 ml of epinine or phenylephrine 0.3%, 1.5% or 3.0% was given as an intracameral injection. The pupils were filmed during 90 seconds with a video camera connected to an operation microscope, and the mean pupil diameters were measured from the video recordings. In 37 additional eyes, 0.15 ml of the vehicle, 1.5% epinine or 1.5% phenylephrine was injected intracamerally, and the eyes were kept on ice overnight. Corneal endothelial morphology was assessed before and after the treatment. Ten eyes were given no injection and served as controls.

    RESULTS. Epinine had a significantly larger mydriatic effect than phenylephrine at equal concentrations. The endothelial cell loss was equal with both substances, and did not exceed that of the vehicle.

    CONCLUSIONS. Epinine was a more potent mydriatic than phenylephrine in this porcine eye model. The porcine eye model appears suitable as a first efficacy screening of substances for intraocular use. Epinine is a promising candidate substance for intraoperative intracameral use in humans, for example in cataract surgery.

  • 46.
    McLoon, Linda K
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 6 Minneapolis, MN 55455.
    Harandi, Vahid M
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Brännstrom, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Liu, Jing-Xia
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wnt and Extraocular Muscle Sparing in Amyotrophic Lateral Sclerosis2014Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 55, nr 9, s. 5482-5496Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: The extraocular muscles (EOM) and their motor neurons are spared in amyotrophic lateral sclerosis (ALS). In limb muscle axon retraction from the neuromuscular junctions occurs early in the disease. Wnts, a conserved family of secreted signaling molecules, play a critical role in neuromuscular junction formation. This is the first study to examine Wnt signaling for its potential involvement in maintenance of normal morphology in EOMs in ALS.

    METHODS: EOM and limb muscle axons, neuromuscular junctions, and myofibers from control, aging, and ALS patients and the SOD1G93A mouse model of ALS were quantified for their expression of Wnt1, Wnt3a, Wnt5a, Wnt7a, and beta-catenin.

    RESULTS: All four Wnt isoforms were expressed in most axon profiles in all human EOMs. Significantly fewer were positive for Wnt1, Wnt3a, and Wnt7a in the human limb muscles. Similar differential patterns in Wnt myofiber expression was also seen, except for Wnt7a, where expression was elevated. In the SOD1G93A mouse, all 4 Wnt isoforms were significantly decreased in the neuromuscular junctions at the terminal stage compared to age matched controls. Beta-catenin was activated in a subset of myofibers in EOM and limb muscle in all patients.

    CONCLUSIONS: The differences in Wnt expression in EOM and limb muscle, particularly at the neuromuscular junction level, suggest that they play a role in the pathophysiology of ALS. Collectively, the data support a role for Wnt signaling in the preservation of the EOM in ALS and their dysregulation and the subsequent development of pathology in the ALS limb muscles.

  • 47. McLoon, Linda K.
    et al.
    Vicente, André
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Fitzpatrick, Krysta R.
    Lindström, Mona
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pedrosa Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Composition, architecture, and functional implications of the connective tissue network of the extraocular muscles2018Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, nr 1, s. 322-329Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: We examined the pattern and extent of connective tissue distribution in the extraocular muscles (EOMs) and determined the ability of the interconnected connective tissues to disseminate force laterally.

    Methods: Human EOMs were examined for collagens I, III, IV, and VI; fibronectin; laminin; and elastin using immunohistochemistry. Connective tissue distribution was examined with scanning electron microscopy. Rabbit EOMs were examined for levels of force transmission longitudinally and transversely using in vitro force assessment.

    Results: Collagens I, III, and VI localized to the endomysium, perimysium, and epimysium. Collagen IV, fibronectin, and laminin localized to the basal lamina surrounding all myofibers. All collagens localized similarly in the orbital and global layers throughout the muscle length. Elastin had the most irregular pattern and ran longitudinally and circumferentially throughout the length of all EOMs. Scanning electron microscopy showed these elements to be extensively interconnected, from endomysium through the perimysium to the epimysium surrounding the whole muscle. In vitro physiology demonstrated force generation in the lateral dimension, presumably through myofascial transmission, which was always proportional to the force generated in the longitudinally oriented muscles.

    Conclusions: A striking connective tissue matrix interconnects all the myofibers and extends, via perimysial connections, to the epimysium. These interconnections are significant and allow measurable force transmission laterally as well as longitudinally, suggesting that they may contribute to the nonlinear force summation seen in motor unit recording studies. This provides strong evidence that separate compartmental movements are unlikely as no region is independent of the rest of the muscle.

  • 48.
    Mönestam, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Long-time outcome of cataract surgery-20 years results from a prospective study2018Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, nr 9Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Purpose: This study reports the change, over a 20-year period, in best-corrected visual acuity (BCVA), subjective visual function (VF-14 questionnaire), and YAG-frequency after cataract surgery.

    Methods: This population-based prospective study reviewed 106 patients (79% of survivors), who underwent cataract surgery during a 1-year period 20 years previously (1997). All patients answered the same visual function questionnaire (VF-14) preoperatively, 4 months postoperatively, 5, 10, 15 and 20 years after surgery. Most patients (90%; 95/106; 70% of survivors) also had a routine ocular examination including BCVA and low contrast visual acuity (VA) 10% and 2.5%. Mean age at the time of surgery was 59 years (range 36-79) and 95% had a three-piece Acrysof® MA60BM implanted.

    Results: Twenty years after surgery the median BCVA of the operated eye had deteriorated to a median of 0.06 (logMAR) (Snellen acuity: 20/23) from 0.0 (logMAR) (20/20) postoperatively, (p=0.001). Sixty-one percent of the patients (58/95) had less than 0.1 logMAR units worsening of BCVA compared with postoperatively. Seventeen percent of the patients (16/95) had worse BCVA 20 years after surgery compared with the preoperative VA. Forty-two percent (45/106) had no deterioration in subjective visual function (VF-14), and mean VF-14 score 20 years after surgery was 92 (range 33-100). The majority of patients (78%;82/106) had 10 points decline or less and 6 percent of the patients (6/106) had a worsening of more than 30 points. 61% of the patients (58/95) had never had Nd:YAG laser capsulotomy. In 7% of the patients (7/95) no cataract surgery had occurred in the fellow eye.

    Conclusions: These prospective population-based, follow-up data provides estimates of extended long-term visual results. The effectiveness of cataract extraction, in offering good long-term visual rehabilitation for the majority of the patients, is confirmed. The extent and distribution of loss in subjective visual function is comparable to the outcome 10 and 15 years after surgery. Age-related macular degeneration remained the most common comorbidity causing large functional loss also 20 years after cataract surgery. Surprisingly, despite the low age at cataract surgery and the long time span, only a minority of patients had needed treatment for posterior capsular opacification.

  • 49. Münch, Mirjam
    et al.
    Léon, Lorette
    Crippa, Sylvain V
    Kawasaki, Aki
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Circadian and wake-dependent effects on the pupil light reflex in response to narrow-bandwidth light pulses2012Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 53, nr 8, s. 4546-4555Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose. Nonvisual light-dependent functions in humans are conveyed mainly by intrinsically photosensitive retinal ganglion cells, which express melanopsin as photopigment. We aimed to identify the effects of circadian phase and sleepiness across 24 hours on various aspects of the pupil response to light stimulation.

    Methods. We tested 10 healthy adults hourly in two 12-hour sessions covering a 24-hour period. Pupil responses to narrow bandwidth red (635 ± 18 nm) and blue (463 ± 24 nm) light (duration of 1 and 30 seconds) at equal photon fluxes were recorded, and correlated with salivary melatonin concentrations at the same circadian phases and to subjective sleepiness ratings. The magnitude of pupil constriction was determined from minimal pupil size. The post-stimulus pupil response was assessed from the pupil size at 6 seconds following light offset, the area within the redilation curve, and the exponential rate of redilation.

    Results. Among the measured parameters, the pupil size 6 seconds after light offset correlated with melatonin concentrations (P < 0.05) and showed a significant modulation over 24 hours with maximal values after the nocturnal peak of melatonin secretion. In contrast, the post-stimulus pupil response following red light stimulation correlated with subjective sleepiness (P < 0.05) without significant changes over 24 hours.

    Conclusions. The post-stimulus pupil response to blue light as a marker of intrinsic melanopsin activity demonstrated a circadian modulation. In contrast, the effect of sleepiness was more apparent in the cone contribution to the pupil response. Thus, pupillary responsiveness to light is under influence of the endogenous circadian clock and subjective sleepiness.

  • 50.
    Ohira, Akihiro
    et al.
    Izumo, Japan.
    Hara, Katsunori
    Izumo, Japan.
    Johannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Tanito, Masaki
    Izumo, Japan.
    Asgrimsdottir, Gudrun Marta
    Reykjavik, Iceland.
    Lund, Sigrun H.
    Reykjavik, Iceland.
    Loftsson, Thorsteinn
    Reykjavik, Iceland.
    Stefansson, Einar
    Reykjavik, Iceland.
    Topical Dexamethasone gamma-Cyclodextrin Nanoparticle Eye Drops increase Visual Acuity and decrease Macular Thickness in Diabetic Macular Edema2015Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, nr 7, artikel-id 2289Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Purpose: To test the efficacy and safety of topical 1.5% dexamethasone γ-cyclodextrin nanoparticle eye drops (dexNP) for diabetic macular edema (DME) and compare to posterior subtenon injection of triamcinolone acetonide.

    Methods: This was a prospective, randomized controlled trial with 22 eyes in 22 consecutive patients with DME, who were randomized to a) topical treatment with dexNP eye drops x3/day for one month, x2/day the next month and finally x1/day the third month or b) one posterior subtenon injection of 20mg triamcinolone acetonide.

    Results: The central macular thickness (CMT) decreased significantly with dexNP eye drops from 483±141mm to 384±142 mm at 4 weeks and 342±114 mm at 8 weeks. For triamcinolone, CMT decreased significantly at all time points. Visual acuity (logMAR) improved significantly with dexNP eye drops from 0.41±0.3 (mean±SD) to 0.32±0.25 and 0.30±0.26 at 4 and 8 weeks respectively. One third of the eye drop group improved more than 0.3 logMAR units. For triamcinolone, logMAR changed significantly from 0.42±0.28 at baseline to 0.32±0.29 at 4 weeks and 0.33±0.37 at 12 weeks. There was a modest increase in IOP at all time points with dexNP eye drops while no increase was seen with triamcinolone. Serum cortisol was affected by both treatments.

    Conclusions: Topical dexamethasone γ-cyclodextrin nanoparticle eye drops significantly improve visual acuity and decrease macular thickness in patients with DME. The effect is similar to that from subtenon triamcinolone as well as to reports on intravitreal steroid implants and triamcinolone intravitreal injections. A modest increase in IOP was seen with the nanoparticle eye drops but IOP normalized after discontinuation of treatment.

12 1 - 50 av 65
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf