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  • 51.
    Bäckström, Gunnie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Redilatation with intracameral mydriatics in phacoemulsification surgery.2006In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 84, no 1, p. 100-104Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To determine whether intracameral mydriatics can redilate pupils that contract during phacoemulsification cataract surgery. METHODS: A total of 80 patients were included in this prospective, randomized, double-blind study performed at Ornsköldsviks Hospital Eye Clinic. Of these, 60 patients had 0.6 microg/ml of epinephrine added to the balanced salt solution (BSS) used for irrigation and 20 patients did not. The patients in each group were randomized and given either an intracameral mydriatics (ICM) solution or placebo intracamerally after phacoemulsification and cortex cleaning. The pupil size was registered preoperatively, after cortex cleaning, 30 seconds after study injection, 2 mins after study injection and the day after surgery. RESULTS: No clinically relevant differences were found preoperatively. In the epinephrine material a significantly longer operation time (p = 0.023) and more procedures requiring Vision Blue and Kelman-type tip in the placebo group might indicate diversity in the grade of cataract. There was a greater degree of contraction in the absence of epinephrine in the irrigation solution (2.3 +/- 1.0 mm in the ICM group and 3.2 +/- 0.7 mm in the placebo group) compared to in the presence of epinephrine. With no epinephrine ICM significantly redilated the pupils at 30 seconds (p < or = 0.001) as well as at 2 mins (p = 0.015). CONCLUSION: We have shown that in cases with an intraoperative pupil contraction, ICM is effective in redilating the pupil. Insufficient adrenergic stimulation of the pupil dilator appears to be a major factor causing intraoperative pupil contraction during phacoemulsification cataract surgery.

  • 52. Celojevic, D
    et al.
    Petersen, A
    Karlsson, J-O
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Zetterberg, M
    Effects of 17β-estradiol on proliferation, cell viability and intracellular redox status in native human lens epithelial cells2011In: Molecular Vision, ISSN 1090-0535, E-ISSN 1090-0535, Vol. 17, p. 1987-1996Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this study was to examine the effects of 17β-estradiol on proliferation, cell death and redox status in cultured human lens epithelial cells (HLECs).

    METHODS: HLECs were exposed to 17β-estradiol after which cell viability was measured by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) and the number of mitotic and apoptotic cell nuclei was determined after staining with Hoechst 33342. Apoptosis was also determined by measuring caspase-3 activity and propidium iodide was used to determine the proportion of non-viable cells. Pro- and antioxidative effects of 17β-estradiol was investigated by measuring peroxides, superoxides and glutathione, using dichlorofluorescein diacetate (DCFH-DA), dihydroethidium (HET), and monochlorobimane (MCB), respectively. Effects on mitochondrial membrane potential were determined using 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolylcarbocyanine iodide (JC-1). The ability of 17β-estradiol to prevent reactive oxygen species (ROS)-production in HLECs after exposure to 25 µM H₂O₂ for 24h was also measured.

    RESULTS: This study demonstrates increased mitotic activity in HLECs exposed to physiologic concentrations of 17β-estradiol (1 nM). Pharmacological concentrations of 17β-estradiol caused increased number of apoptotic cell nuclei and caspase-3 activation. Physiologic concentrations of 17β-estradiol (0.1-10 nM) stabilized the mitochondrial membrane potential. Similar or slightly higher concentrations of 17β-estradiol (0.01-1 µM) protected against H₂O₂-induced oxidative stress as evident by decreased levels of peroxides and superoxides.

    CONCLUSIONS: The present study demonstrates mitogenic and anti-oxidative effects of 17β-estradiol at physiologic concentrations, whereas pharmacological levels induced oxidative stress and acted pro-apoptotic in cultured lens cells.

  • 53. Celojevic, Dragana
    et al.
    Nilsson, Staffan
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tasa, Gunnar
    Juronen, Erkki
    Karlsson, Jan-Olof
    Zetterberg, Henrik
    Petersen, Anne
    Zetterberg, Madeleine
    Superoxide dismutase gene polymorphisms in patients with age-related cataract2013In: Ophthalmic Genetics, ISSN 1381-6810, E-ISSN 1744-5094, Vol. 34, no 3, p. 140-145Article in journal (Refereed)
    Abstract [en]

    Background: Functional polymorphisms in genes encoding antioxidant enzymes may result in reduced enzyme activity and increased levels of reactive oxygen species, such as superoxide radicals, which in turn may contribute to increased risk of age-related disorders. Copper-zinc superoxide dismutases, SOD-1 and SOD-3, and manganese superoxide dismutase, SOD-2, are enzymes involved in the protection against oxidative stress and detoxification of superoxide. In this study, we investigated a number of disease-associated single nucleotide polymorphisms (SNPs) of SOD1, SOD2 and SOD3, in patients with age-related cataract.

    Materials and methods: The study included an Estonian sample of 492 patients with age-related cataract, subgrouped into nuclear, cortical, posterior subcapsular and mixed cataract, and 185 controls. Twelve SNPs in SOD1, SOD2 and SOD3 were genotyped using TaqMan Allelic Discrimination. Haplotype analysis was performed on the SNPs in SOD2.

    Results: None of the studied SNPs showed an association with risk of cataract. These results were consistent after adding known risk factors (age, sex and smoking) as covariates in the multivariate analyses and after stratification by cataract subtype. Analysis of SOD2 haplotypes did not show any associations with risk of cataract.

    Conclusions: If genetic variation in genes encoding SOD-1, SOD-2 and SOD-3 contributes to cataract formation, there is no major contribution of the SNPs analyzed in the present study.

  • 54. Chang, Anthony
    et al.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Ronbeck, Margrethe
    Kugelberg, Maria
    Comparison of posterior capsule opacification and glistenings with 2 hydrophobic acrylic intraocular lenses: 5-to 7-year follow-up2013In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 39, no 5, p. 694-698Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To compare posterior capsule opacification (PCO) and glistenings 5 to 7 years after cataract surgery with implantation of 2 hydrophobic acrylic intraocular lenses (IOLs) and evaluate the effects on corrected distance visual acuity (CDVA) and contrast sensitivity. SETTING: St. Erik Eye Hospital, Stockholm, Sweden. DESIGN: Randomized clinical trial. METHODS: Cataract surgery with standard phacoemulsification was performed in 1 eye of patients. The patients were randomized to an Acrysof SA60AT (1-piece IOL group) or a Sensar AR40e (3-piece IOL group), both hydrophobic acrylic IOLs with a sharp-edged design. Five to 7 years postoperatively, retroillumination images were obtained and the PCO area and severity (area affected within the capsulorhexis and severity) were evaluated using computer software. High-contrast (100%) and low-contrast (2.5%) CDVAs were measured. The neodymium:YAG laser capsulotomy rates were recorded. Scheimpflug images were obtained to evaluate glistenings, which were graded subjectively at the slitlamp and quantified objectively by digital image analysis using computer software. RESULTS: The study enrolled 80 patients. There were no significant differences in PCO between the 2 groups. The 3-piece IOL group had significantly fewer glistenings (P<.001). There was good correlation between the subjective grading of glistenings and objective computer-processed image grading. The glistenings were not correlated with IOL power, CDVA, or contrast sensitivity. CONCLUSIONS: There were no significant differences in PCO between the 2 acrylic hydrophobic IOLs 5 to 7 years postoperatively. The 1-piece IOL group developed more glistenings than the 3-piece IOL group.

  • 55.
    Chen, Jialin
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Chen, Peng
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Zhou, Qingjun
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Ciliary Neurotrophic Factor Promotes the Migration of Corneal Epithelial Stem/progenitor Cells by Up-regulation of MMPs through the Phosphorylation of Akt2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 25870Article in journal (Refereed)
    Abstract [en]

    The migration of limbal epithelial stem cells is important for the homeostasis and regeneration of corneal epithelium. Ciliary neurotrophic factor (CNTF) has been found to promote corneal epithelial wound healing by activating corneal epithelial stem/progenitor cells. However, the possible effect of CNTF on the migration of corneal epithelial stem/progenitor cells is not clear. This study found the expression of CNTF in mouse corneal epithelial stem/progenitor cells (TKE2) to be up-regulated after injury, on both gene and protein level. CNTF promoted migration of TKE2 in a dose-dependent manner and the peak was seen at 10 ng/ml. The phosphorylation level of Akt (p-Akt), and the expression of MMP3 and MMP14, were up-regulated after CNTF treatment both in vitro and in vivo. Akt and MMP3 inhibitor treatment delayed the migration effect by CNTF. Finally, a decreased expression of MMP3 and MMP14 was observed when Akt inhibitor was applied both in vitro and in vivo. This study provides new insights into the role of CNTF on the migration of corneal epithelial stem/progenitor cells and its inherent mechanism of Up-regulation of matrix metalloproteinases through the Akt signalling pathway.

  • 56.
    Chen, Jialin
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Zhang, Wei
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kelk, Peyman
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mechanical stress potentiates the differentiation of periodontal ligament stem cells into keratocytes2018In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 102, no 4, p. 562-569Article in journal (Refereed)
    Abstract [en]

    Aims To explore the role of corneal-shaped static mechanical strain on the differentiation of human periodontal ligament stem cells (PDLSCs) into keratocytes and the possible synergistic effects of mechanics and inducing medium. Methods PDLSCs were exposed to 3% static dome-shaped mechanical strain in a Flexcell Tension System for 3 days and 7 days. Keratocyte phenotype was determined by gene expression of keratocyte markers. Keratocyte differentiation (inducing) medium was introduced in the Flexcell system, either continuously or intermittently combined with mechanical stimulation. The synergistic effects of mechanics and inducing medium on keratocyte differentiation was evaluated by gene and protein expression of keratocyte markers. Finally, a multilamellar cell sheet was assembled by seeding PDLSCs on a collagen membrane and inducing keratocyte differentiation. The transparency of the cell sheet was assessed, and typical markers of native human corneal stroma were evaluated by immunofluorescence staining. Results Dome-shaped mechanical stimulation promoted PDLSCs to differentiate into keratocytes, as shown by the upregulation of ALDH3A1, CD34, LUM, COL I and COL V. The expression of integrins were also upregulated after mechanical stimulation, including integrin alpha 1, alpha 2, beta 1 and non-muscle myosin II B. A synergistic effect of mechanics and inducing medium was found on keratocyte differentiation. The cell sheets were assembled under the treatment of mechanics and inducing medium simultaneously. The cell sheets were transparent, multilamellar and expressed typical markers of corneal stroma. Conclusion Dome-shaped mechanical stimulation promotes differentiation of PDLSCs into keratocytes and has synergistic effects with inducing medium. Multilamellar cell sheets that resemble native human corneal stroma show potential for future clinical applications.

  • 57.
    Chen, Jialin
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Zhang, Wei
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Kelk, Peyman
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Substance P and patterned silk biomaterial stimulate periodontal ligament stem cells to form corneal stroma in a bioengineered three-dimensional model2017In: Stem Cell Research & Therapy, E-ISSN 1757-6512, Vol. 8, article id 260Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to generate a bioengineered multi-lamellar human corneal stroma tissue in vitro by differentiating periodontal ligament stem cells (PDLSCs) towards keratocytes on an aligned silk membrane.

    Methods: Human PDLSCs were isolated and identified. The neuropeptide substance P (SP) was added in keratocyte differentiation medium (KDM) to evaluate its effect on keratocyte differentiation of PDLSCs. PDLSCs were then seeded on patterned silk membrane and cultured with KDM and SP. Cell alignment was evaluated and the expression of extracellular matrix (ECM) components of corneal stroma was detected. Finally, multi-lamellar tissue was constructed in vitro by PDLSCs seeded on patterned silk membranes, which were stacked orthogonally and stimulated by KDM supplemented with SP for 18 days. Sections were prepared and subsequently stained with hematoxylin and eosin or antibodies for immunofluorescence observation of human corneal stroma-related proteins.

    Results: SP promoted the expression of corneal stroma-related collagens (collagen types I, III, V, and VI) during the differentiation induced by KDM. Patterned silk membrane guided cell alignment of PDLSCs, and important ECM components of the corneal stroma were shown to be deposited by the cells. The constructed multi-lamellar tissue was found to support cells growing between every two layers and expressing the main type of collagens (collagen types I and V) and proteoglycans (lumican and keratocan) of normal human corneal stroma.

    Conclusions: Multi-lamellar human corneal stroma-like tissue can be constructed successfully in vitro by PDLSCs seeded on orthogonally aligned, multi-layered silk membranes with SP supplementation, which shows potential for future corneal tissue engineering.

  • 58. Claesson, Margareta
    et al.
    Armitage, W John
    Byström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Montan, Per
    Samolov, Branka
    Stenvi, Ulf
    Lundström, Mats
    Validation of Catquest-9SF - A Visual Disability Instrument to Evaluate Patient Function After Corneal Transplantation2017In: Cornea, ISSN 0277-3740, E-ISSN 1536-4798, Vol. 36, no 9, p. 1083-1088Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Catquest-9SF is a 9-item visual disability questionnaire developed for evaluating patient-reported outcome measures after cataract surgery. The aim of this study was to use Rasch analysis to determine the responsiveness of Catquest-9SF for corneal transplant patients.

    METHODS: Patients who underwent corneal transplantation primarily to improve vision were included. One group (n = 199) completed the Catquest-9SF questionnaire before corneal transplantation and a second independent group (n = 199) completed the questionnaire 2 years after surgery. All patients were recorded in the Swedish Cornea Registry, which provided clinical and demographic data for the study. Winsteps software v.3.91.0 (Winsteps.com, Beaverton, OR) was used to assess the fit of the Catquest-9SF data to the Rasch model.

    RESULTS: Rasch analysis showed that Catquest-9SF applied to corneal transplant patients was unidimensional (infit range, 0.73-1.32; outfit range, 0.81-1.35), and therefore, measured a single underlying construct (visual disability). The Rasch model explained 68.5% of raw variance. The response categories of the 9-item questionnaire were ordered, and the category thresholds were well defined. Item difficulty matched the level of patients' ability (0.36 logit difference between the means). Precision in terms of person separation (3.09) and person reliability (0.91) was good. Differential item functioning was notable for only 1 item (satisfaction with vision), which had a differential item functioning contrast of 1.08 logit.

    CONCLUSIONS: Rasch analysis showed that Catquest-9SF is a valid instrument for measuring visual disability in patients who have undergone corneal transplantation primarily to improve vision.

  • 59.
    Claesson, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Johansson, Magdalena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mydriasis with different preparations of topically administered lidocaine hydrochloride2009In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 35, no 2, p. 277-281Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To quantify the mydriatic effect and side effects of topical lidocaine hydrochloride with different pH values and concentrations in healthy volunteers.

    SETTING: Umeå University Hospital Eye Clinic, Umeå, Sweden.

    METHODS: In this intraindividual comparison double-masked randomized study, healthy volunteers were given topical lidocaine 8%, lidocaine 8% pH 6.0, or a placebo 3 times at 90-second intervals. Thereafter, a drop of tropicamide 0.5% or placebo was given (tropicamide setting). Another group of healthy volunteers was given topical lidocaine 4%, 8%, or 16% 3 or 6 times at 90-second intervals (dose-response setting). Before and 15, 30, 60, and 180 minutes after eyedrop instillation, the near point was determined and Scheimpflug photography was performed.

    RESULTS: The tropicamide setting comprised 26 volunteers (mean age 23.5 years) and the dose-response setting, 10 volunteers (mean age 24.5 years). The direct mydriatic effect of lidocaine was larger at pH 6.0 (mean peak effect 0.61+/-0.06 [SEM] versus 0.42+/-0.04 mm) (P< .05), and the augmentation of tropicamide mydriasis was larger at pH 6.0. Lidocaine 8% had a better direct mydriatic effect than lidocaine 4% and lidocaine 16% (mean peak effect 0.60+/-0.09 mm versus 0.19+/-0.08 mm and 0.28+/-0.10 mm, respectively) (P< .01). Lidocaine 16% given 6 times caused corneal side effects.

    CONCLUSIONS: Lidocaine 8% with pH 6.0 had a maximum direct mydriatic effect and gave maximum augmentation of tropicamide mydriasis without causing unwanted corneal side effects and thus should be preferable for topical anesthesia in cataract surgery.

  • 60. Crippa, Sylvain, V
    et al.
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kawasaki, Aki
    Chromatic pupillometry in children2018In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, article id 669Article in journal (Refereed)
    Abstract [en]

    Chromatic pupillometry is a technique that is increasingly used to assess retinal disorders. As age may be one of the various factors which can influence the pupillary light reaction, this study aimed to evaluate the pupil responses to colored light stimuli in the pediatric population. Fifty-three children with normal vision and without any history of ocular disorders were tested with a portable pupillometer. Four test sequences were used: five dim blue (470 nm) stimuli presented in half log steps ranging from -3.15 to -1.15 log cd/m(2) after 3 min of dark adaptation, five red (622 nm) stimuli of -1.15, -0.7, -0.15, 0.3, and 0.85 log cd/m(2) after 1 min light adaptation, one bright blue stimulus of 2.2 log cd/m(2) and one bright red of 2 log cd/m(2). The results were grouped by age: a younger group included 27 children aged from 3 to 10 years old and an older group included 26 from 10 and 1 month to 18 years old. The younger group had a smaller pupil diameter after dark adaptation compared with the older group. A linear regression defining the photopic threshold showed that younger subjects had a higher threshold, e.g., needed a brighter red stimulus to evoke a threshold pupil response comparable that of subjects. Age thus seems to influence outer retinal sensitivity at least as evaluated by the pupillary photopic threshold intensity. The post-illumination pupillary reaction was used as a marker of intrinsic melanopsin activity and did not show any difference between the two age groups.

  • 61. Czajka, Marcin
    et al.
    Byhr, Eva
    Olivestedt, Goran
    Olofsson, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Endophthalmitis after small-gauge vitrectomy: A retrospective case series2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92 4 254, p. 10-10Article in journal (Other academic)
  • 62. Czajka, Marcin Piotr
    et al.
    Byhr, Eva
    Olivestedt, Göran
    Olofsson, Eva M.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Endophthalmitis after small-gauge vitrectomy: a retrospective case series from Sweden2016In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 94, no 8, p. 829-835Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the anatomical and functional outcomes of acute-onset endophthalmitis after small-gauge vitrectomy. Methods: Retrospective case series of patients who underwent 23- or 25-gauge vitrectomy at four centres in Sweden between 2008 and 2012. Postvitrectomy endophthalmitis was identified through the search of the journal records of each institution, and the diagnosis was based on clinical criteria regardless of culture results. Results: Twenty-four patients (24 eyes) were included. The incidence of endophthalmitis following small-gauge vitrectomy was 0.14%. Indications for small-gauge vitrectomy enclosed epiretinal membrane (n=13), retinal detachment (n=5) and others (n=6). Surgical technique included 23- and 25-gauge vitrectomy (23:1). Four eyes had sutured sclerotomies, and two had postoperative hypotony <7mmHg. Days to endophthalmitis presentation varied between 1 and 21 (mean 66). Treatment methods included the following: tap and antibiotic injection (n=7), tap, antibiotic injection with subsequent vitrectomy (n=2) and prompt vitrectomy with antibiotics (n=15). Sixteen eyes (66.7%) were culture positive, whereas the other eight cases were culture negative. Anatomical results included evisceration (n=1), phthisis (n=1), and globe intact (n=22). Presenting best corrected visual acuity (BCVA) were hand motion (n=14), light perception (n=7), counting fingers (n=2), and no data (n=1). Functionally 19 eyes (79%) had Snellen VA 0.1; 11 eyes (46%) had VA 0.5 Mean logMar BCVA preoperatively and at the last follow-up were 2.07 +/- 0.6 and 0.79 +/- 0.99, respectively. Conclusions: In spite of good anatomical and functional results, this study showed higher rate of endophthalmitis than the latest reports suggesting that small-gauge vitrectomy has reached the safety level of standard 20-gauge vitrectomy when infectious endophthalmitis is concerned.

  • 63.
    Danielsson, Adam
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The effect of ALS on 2 extraocular muscle fiber 3 composition.2015Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 64.
    Domellöf, Fatima Pedrosa
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Parkkonen, Kimmo
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindström, Mona
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Nord, Hanna
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    von Hoffsten, Jonas
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Li, Zhenlin
    Univ Paris 06, CNRS, INSERM, Inst Biol Paris Seine, Paris, France.
    Desmin in extraocular muscles2015In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 7Article in journal (Other academic)
  • 65.
    Domellöf, Fatima Pedrosa
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Rodriguez Garcia, Maria Angels
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Vicente, André
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Sandgren Hochhard, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Sarcomere remodelling and gene expression profile changes following strabismus surgery2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal (Other academic)
    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.

  • 66.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindahl, Olof A.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    An applanation resonator sensor for measuring intraocular pressure using combined continuous force and area measurement2003In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, no 7, p. 3017-3024Article in journal (Refereed)
  • 67.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Holmlund, Petter
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    The Pressure Difference between Eye and Brain Changes with Posture2016In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 80, no 2, p. 269-276Article in journal (Refereed)
    Abstract [en]

    Objective: The discovery of a posture-dependent effect on the difference between intraocular pressure (IOP) and intracranial pressure (ICP) at the level of lamina cribrosa could have important implications for understanding glaucoma and idiopathic intracranial hypertension and could help explain visual impairments in astronauts exposed to microgravity. The aim of this study was to determine the postural influence on the difference between simultaneously measured ICP and IOP.

    Methods: Eleven healthy adult volunteers (age = 46 ± 10 years) were investigated with simultaneous ICP, assessed through lumbar puncture, and IOP measurements when supine, sitting, and in 9° head-down tilt (HDT). The trans–lamina cribrosa pressure difference (TLCPD) was calculated as the difference between the IOP and ICP. To estimate the pressures at the lamina cribrosa, geometrical distances were estimated from magnetic resonance imaging and used to adjust for hydrostatic effects.

    Results: The TLCPD (in millimeters of mercury) between IOP and ICP was 12.3 ± 2.2 for supine, 19.8 ± 4.6 for sitting, and 6.6 ± 2.5 for HDT. The expected 24-hour average TLCPD on earth—assuming 8 hours supine and 16 hours upright—was estimated to be 17.3mmHg. By removing the hydrostatic effects on pressure, a corresponding 24-hour average TLCPD in microgravity environment was simulated to be 6.7mmHg.

    Interpretation: We provide a possible physiological explanation for how microgravity can cause symptoms similar to those seen in patients with elevated ICP. The observed posture dependency of TLCPD also implies that assessment of the difference between IOP and ICP in upright position may offer new understanding of the pathophysiology of idiopathic intracranial hypertension and glaucoma. 

  • 68.
    el Azazi, Mildred
    et al.
    S:t Erik, Stockholm.
    Wang, Ling
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wachtmeister, Lillemor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Background light adaptation of the retinal neuronal adaptive system. II. Dynamic effects2004In: Documenta Ophthalmologica, ISSN 0012-4486, Vol. 109, no 2, p. 201-213Article in journal (Refereed)
    Abstract [en]

    The dynamic effects of continuous exposure to light on the neuronal adaptive system of the retina, as indicated by the oscillatory response (OPs) of the electroretinogram (ERG) were studied in the albino rat. Digitally filtered OPs and the a- and b-waves of the corneal ERG were simultaneously recorded in dark adaptation, during continuous light adaptation to four levels of background light (BGL) changing in steps of two log units from 1.43 x 10(-6) cd/m2, referred to as 'low and high scotopic, low and high mesopic' levels. Exposed to 'high scotopic' BGL the total oscillatory response (SOP) significantly enhanced within the first minute, whereas the amplitudes of the a- and b-waves were unaffected. In 'low mesopic' BGL the SOP increased within the first minute, whereas the a- and b-waves significantly decreased. 'High mesopic' BGL instantaneously and profoundly reduced both the SOP and the slow potentials. The individual OPs changed in amplitudes mainly within the first minute of BGL. In general, the earlier OPs (O1 and O2) reacted more to the two 'scotopic' BGL levels, whereas the later OPs (O3 and 04) were more affected by the relatively brighter two 'mesopic' conditions. In conclusion, the rapid increase of the OPs within the first minute of 'high scotopic' and 'low mesopic' BGL exposure may represent a rudimentary light adaptational effect in the rod-dominated rat retina. These findings also suggest that the neuronal adaptive mechanism of the retina seems to be a robust system, probably attaining preservation of visual abilities in the rat on exposure to light.

  • 69.
    Engren, Anna-Lotta
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Anterior Chamber Depth Measurements and Refractive Outcome in Cataract Surgery2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 70.
    Engren, Anna-Lotta
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Anterior chamber depth, intraocular lens position, and refractive outcomes after cataract surgery2013In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 39, no 4, p. 572-577Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To assess postoperative intraocular lens (IOL) position in relation to the cornea and iris, compare 2 devices for anterior chamber depth (ACD) measurement, and assess the impact of these factors on postoperative refraction in phacoemulsification. SETTING: Department of Clinical Sciences/Ophthalmology, Umea University Hospital, Umea Sweden. DESIGN: Evaluation of diagnostic test or technology. METHODS: Biometry and measurement of the anterior segment were performed preoperatively and postoperatively with the partial coherence interferometry (PCI)-based IOLMaster and the Pentacam HR Scheimpflug device. Predicted refraction was calculated with ACD estimations according to the Haigis formula and was compared with the actual postoperative refraction. Changes in ACD and the distance between the cornea-iris and the iris-lens/IOL were assessed from Scheimpflug images. The theoretical refractive impact of differences in ACD was calculated. RESULTS: The mean preoperative ACD and refractive prediction error, respectively, was 3.22 mm +/- 0.37 (SD) and 0.41 +/- 0.43 diopters (D) for the PCI device and 3.21 +/- 0.35 mm and 0.41 +/- 0.41 D for the Scheimpflug device; the difference was not statistically significant. The mean ACD, cornea-iris distance, and iris-lens/IOL distance changes were 1.62 +/- 0.38 mm, 0.78 +/- 0.29 mm, and 0.85 +/- 0.27 mm, respectively. The mean predicted refractive outcome from a 1.0 mm difference in ACD was 0.32 D. CONCLUSIONS: No difference was found between the measurement devices. Although the exact postoperative IOL position is difficult to predict, its impact on postoperative refraction was comparatively small compared with the impact of minor corneal curvature or axial length measurement errors.

  • 71. Farhoudi, Daniel B.
    et al.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mollazadegan, Kaziwe
    Montan, Per
    Lundström, Mats
    Kugelberg, Maria
    Spectacle use after routine cataract surgery and vision-related activity limitation2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, no 6, p. 582-585Article in journal (Refereed)
    Abstract [en]

    Purpose: To explore the relationship between acquisition of new spectacles after routine cataract surgery and vision‐related activity limitation (VRAL) postoperatively.

    Methods: This cohort study with intervention (survey) included 1329 patients in Sweden who had undergone a second‐eye cataract surgery during March 2013. Data from the Swedish National Cataract Register were used, including evaluations of VRAL through the Catquest‐9SF questionnaire before and 3 months after cataract surgery. Five months after the second‐eye surgery, patients completed another five‐item questionnaire about spectacle use preoperatively and postoperatively including an item on surgeons’ advice about the need for spectacles. These responses were linked to the Rasch‐analysed Catquest‐9SF data to identify correlations with VRAL.

    Results: A total of 1239 patients finally participated in the study after excluding those who did not fulfil the inclusion criteria. Patients who were advised about the need for spectacles postoperatively (n = 387) had a greater (p = 0.039) improvement in the postoperative VRAL compared to patients who were not advised (n = 691). Patients who obtained new spectacles postoperatively (n = 512) also had greater improvement (p = 0.032) compared to those who did not (n = 724).

    Conclusion: The average improvements in the VRAL after surgery were significantly higher for patients who obtained new distance spectacles postoperatively and for patients who were informed about the need for spectacles by their practitioners.

  • 72.
    Fong, Gloria
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada.
    Backman, Ludvig J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    Scott, Alex
    Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The Effects of Substance P and Acetylcholine on Human Tenocyte Proliferation Converge Mechanistically via TGF-β12017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174101Article in journal (Refereed)
    Abstract [en]

    Previous in vitro studies on human tendon cells (tenocytes) have demonstrated that the exogenous administration of substance P (SP) and acetylcholine (ACh) independently result in tenocyte proliferation, which is a prominent feature of tendinosis. Interestingly, the possible link between SP and ACh has not yet been explored in human tenocytes. Recent studies in other cell types demonstrate that both SP and ACh independently upregulate TGF-β1 expression via their respective receptors, the neurokinin 1 receptor (NK-1R) and muscarinic ACh receptors (mAChRs). Furthermore, TGF-β1 has been shown to downregulate NK-1R expression in human keratocytes. The aim of this study was to examine if TGF-β1 is the intermediary player involved in mediating the proliferative pathway shared by SP and ACh in human tenocytes. The results showed that exogenous administration of SP and ACh both caused significant upregulation of TGF-β1 at the mRNA and protein levels. Exposing cells to TGF-β1 resulted in increased cell viability of tenocytes, which was blocked in the presence of the TGFβRI/II kinase inhibitor. In addition, the proliferative effects of SP and ACh on tenocytes were reduced by the TGFβRI/II kinase inhibitor; this supports the hypothesis that the proliferative effects of these signal substances are mediated via the TGF-β axis. Furthermore, exogenous TGF-β1 downregulated NK-1R and mAChRs expression at both the mRNA and protein levels, and these effects were negated by simultaneous exposure to the TGFβRI/II kinase inhibitor, suggesting a negative feedback loop. In conclusion, the results indicate that TGF-β1 is the intermediary player through which the proliferative actions of both SP and ACh converge mechanistically.

  • 73.
    Fredriksson, Anneli
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The multifocal wavefront in Keratoconus. A Study based on ray tracing wavefront aberrometry.2015Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 74.
    Fredriksson, Anneli
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Measurement centration and zone diameter in anterior, posterior and total corneal astigmatism in keratoconus2017In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 95, no 8, p. 826-833Article in journal (Refereed)
    Abstract [en]

    Purpose To investigate the central and paracentral astigmatism and the significance of centration and measurement zone diameter compared to a 3-mm pupil-centred measurement zone in keratoconus and in healthy eyes.

    Methods Twenty-eight right eyes from 28 KC patients with an inferotemporal cone were selected according to specified criteria based on Oculus Pentacam HR (R) measurements and were matched with healthy control eyes. The flat (K1) and steep (K2) keratometry readings were registered from the Total Corneal Refractive Power' (TCRP) display as well as the anterior and posterior corneal astigmatism displays (ACA and PCA, respectively). Astigmatic power vectors KP0 and KP45 were calculated and analysed for a 6-mm and two 3-mm zones centred on the corneal apex and the pupil, and for 8 paracentral 3-mm zones.

    Results The astigmatism was generally higher in KC. Many astigmatic values in KC differed between the 3-mm pupil-centred and the 3- and 6-mm apex-centred zones in KC. In the controls, no corresponding differences between measurement zones were seen, apart from PCA, which differed. The magnitude and direction of KP0 and KP45 varied greatly between the paracentral measurements in KC.

    Conclusion Centration and measurement zone diameter have great impacts on the astigmatic values in KC. A small pupil-centred measurement zone should be considered when evaluating the astigmatism in KC.

  • 75.
    Goldsteins, Gundars
    et al.
    Umeå University, Faculty of Medicine, Molecular Biology.
    Andersson, Karin
    Umeå University, Faculty of Medicine, Molecular Biology.
    Olofsson, Anders
    Umeå University, Faculty of Medicine, Molecular Biology.
    Dacklin, Ingrid
    Umeå University, Faculty of Medicine, Molecular Biology.
    Edvinsson, Åsa
    Umeå University, Faculty of Medicine, Molecular Biology.
    Baranov, Vladimir
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Thylén, Christina
    Umeå University, Faculty of Medicine, Molecular Biology.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Lundgren, Erik
    Umeå University, Faculty of Medicine, Molecular Biology.
    Characterisation of two highly amyloidogenic mutants of transthyretin.1997In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 36, no 18, p. 5346-5352Article in journal (Refereed)
    Abstract [en]

    The plasma protein transthyretin (TTR) has the potential to form amyloid under certain conditions. More than 50 different point mutations have been associated with amyloid formation that occurs only in adults. It is not known what structural changes are introduced into the structure of this otherwise stable molecule that results in its aggregation into insoluble amyloid fibrils. On the basis of calculations of the frequency of known mutations over the polypeptide, we have constructed two mutants in the D-strand of the polypeptide. These molecules, containing either a deletion or a substitution at amino acid positions 53−55, were unstable and spontaneously formed aggregates upon storage in TBS (pH 7.6). The precipitates were shown to be amyloid by staining with thioflavin T and Congo Red. Their ultrastructure was very similar to that of amyloid fibrils deposited in the vitreous body of patients with familial amyloidotic polyneuropathy type 1 with an amino acid replacement in position 30 (TTRmet30). Like amyloid isolated from the vitreous body of the eye, the amyloid precipitates generated from the TTR mutants exposed a trypsin cleavage site between amino acid residues 48 and 49, while plasma TTRmet30 isolated from amyloidosis patients as well as wild-type TTR only showed minor trypsin sensitivity. Our data indicate that the mutants we have constructed are similar to amyloid precursors or may share structural properties with intermediates on a pathway leading to amyloid deposits of plasma TTR.

  • 76.
    Golovleva, Irina
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Bhattacharya, Sanjoy
    Wu, Zhiping
    Shaw, Natacha
    Yang, Yanwu
    Andrabi, Khurshid
    West, Karen A
    Burstedt, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Forsman, Kristina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Holmgren, Gösta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Noy, Noa
    Quin, Jun
    Crabb, John W
    Disease-causing mutations in the cellular retinaldehyde binding protein tighten and abolish ligand interactions2003In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 278, no 14, p. 12397-12402Article in journal (Refereed)
    Abstract [en]

    Mutations in the human cellular retinaldehyde binding protein (CRALBP) gene cause retinal pathology. To understand the molecular basis of impaired CRALBP function, we have characterized human recombinant CRALBP containing the disease causing mutations R233W or M225K. Protein structures were verified by amino acid analysis and mass spectrometry, retinoid binding properties were evaluated by UV-visible and fluorescence spectroscopy and substrate carrier functions were assayed for recombinant 11-cis-retinol dehydrogenase (rRDH5). The M225K mutant was less soluble than the R233W mutant and lacked retinoid binding capability and substrate carrier function. In contrast, the R233W mutant exhibited solubility comparable to wild type rCRALBP and bound stoichiometric amounts of 11-cis- and 9-cis-retinal with at least 2-fold higher affinity than wild type rCRALBP. Holo-R233W significantly decreased the apparent affinity of rRDH5 for 11-cis-retinoid relative to wild type rCRALBP. Analyses by heteronuclear single quantum correlation NMR demonstrated that the R233W protein exhibits a different conformation than wild type rCRALBP, including a different retinoid-binding pocket conformation. The R233W mutant also undergoes less extensive structural changes upon photoisomerization of bound ligand, suggesting a more constrained structure than that of the wild type protein. Overall, the results show that the M225K mutation abolishes and the R233W mutation tightens retinoid binding and both impair CRALBP function in the visual cycle as an 11-cis-retinol acceptor and as a substrate carrier.

  • 77.
    Golovleva, Irina
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Jonsson, Frida
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Burstedt, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Heterogeneity and complexity of EYS mutations in autosomal recessive retinitis pigmentosa in northern Sweden2016In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 12Article in journal (Refereed)
  • 78.
    Golovleva, Irina
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Köhn, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Burstedt, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Daiger, Stephen
    The University of Texas Health Science Center Houston, Human Genetics Center.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Mutation spectra in autosomal dominant and recessive retinitis pigmentosa in northern sweden.2010In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 664, p. 255-262Article in journal (Refereed)
    Abstract [en]

    Retinal degenerations represent a heterogeneous group of disorders affecting the function of the retina. The frequency of retinitis pigmentosa (RP) is 1/3500 worldwide, however, in northern Sweden it is 1/2000 due to limited migration and a 'founder' effect. In this study we identified genetic mechanisms underlying autosomal dominant and recessive RP present in northern Sweden. Several novel mutations unique for this region were found. In an autosomal recessive form of RP, Bothnia dystrophy caused by mutations in the RLBP1 gene, bi-allelic mutations R234W, M226K and compound heterozygosity, M226K+R234W was detected.In dominant form of RP mapped to 19q13.42 a 59 kb genomic deletion including the PRPF31 and three other genes was found.These data provide additional information on the molecular mechanisms of RP evolvement and in the future might be useful in development of therapeutic strategies. Identification of the disease-causing mutations allowed introducing molecular genetic testing of the patients and their families into the clinical practice.

  • 79.
    Granberg, I
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Lindell, Björn
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Eriksson, Per-Olof
    Umeå University, Faculty of Medicine, Department of Odontology, Clinical Oral Physiology.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Capillary supply in relation to myosin heavy chain fibre composition of human intrinsic tongue muscles2010In: Cells Tissues Organs, ISSN 1422-6405, E-ISSN 1422-6421, Vol. 192, no 5, p. 303-313Article in journal (Refereed)
    Abstract [en]

    The capillary supply and myosin heavy chain (MyHC) composition of three different intrinsic tongue muscles was analysed in the anterior and posterior regions of the human tongue with biochemical and immunohistochemical techniques. Mean capillary density for the whole tongue was 796 ± 82 cap/mm², without regional differences. The overall number of capillaries around each fibre (CAF) was higher in the posterior than in the anterior region (2.5 vs. 2.1, p = 0.009). However, correcting for regional differences in fibre size, CAF per fibre area was higher in the anterior region (4.3 vs. 3.0, p < 0.001). Muscle fibres containing fast MyHCs predominated in the anterior region (78.7%), consisting of MyHCIIa (58.5%), MyHCIIx (1.0%), MyHCIIa+MyHCIIx (11.3%) and MyHCI+MyHCIIa (7.9%). Fibres containing slow MyHC predominated in the posterior region (65.2%), consisting of MyHCI (45.5%) and MyHCI+MyHCIIa (19.7%). A minor fibre population (<2%) contained unusual MyHC isoforms, namely MyHC foetal, MyHC slow-tonic, MyHC α-cardiac or MyHC embryonic. The microvascularization of the human tongue was twice as high as in human limb muscles. Regional similarities in capillary supply, but differences in fibre phenotype composition, suggest that human tongue muscle fibres are fatigue resistant independently of MyHC content. High frequency of hybrid fibres, that is fibres co-expressing two or more MyHC isoforms, indicates a wider spectrum of fibre contractile properties than in limb muscles. In conclusion, human intrinsic tongue muscles showed internal specialization in distribution of MyHC isoforms and capillary supply, but not in the expression of unusual MyHCs.

  • 80. Granstam, Elisabet
    et al.
    Westborg, Inger
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Barkander, Anna
    Börjesson, Malin
    Lindahl, Sara
    Meszaros, Eva
    Wojciechowska-Zajac, Anna
    Wagner, Philippe
    Albrecht, Susanne
    Karlsson, Niklas
    Bjärnhall, Gunilla
    Lövestam-Adrian, Monica
    Reduced occurrence of severe visual impairment after introduction of anti-Vascular Endothelial Growth Factor in wet age-related macular degeneration: a population- and register-based study from northern Sweden2016In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 94, no 7, p. 646-651Article in journal (Refereed)
    Abstract [en]

    Purpose To study the occurrence of severe visual impairment (SVI) and treatment outcome at 12months in patients treated for wet age-related macular degeneration (AMD) by use of data from the Swedish Macula Register (SMR) and referrals to the regional low vision clinics in five northern counties.

    Methods Referrals to low vision clinics during 2005, 2009 and 2013 and treatment outcome at 12months from the SMR database from 2008 until 2013 in patients >65years of age in five northern counties were included in the survey.

    Results The rate of referral due to AMD was significantly reduced during the time period (-48%; p<0.001). At 12months, a significant slight mean improvement in logMAR visual acuity (VA) was observed (-0.01, SD 0.37; p<0.001) after a mean of 5.02.3 anti-vascular endothelial growth factor (VEGF)-injections were administered. Age and low baseline VA was associated with less favourable visual outcome (p<0.001).

    Conclusion Referral rate to low vision clinic is a valuable tool for estimating occurrence of SVI and fell between the years 2005 until 2013. Data from the SMR showed improvement in visual acuity on the whole, but also identified patients at high risk for developing SVI during anti-VEGF-treatment.

  • 81. Grzybowski, Andrzej
    et al.
    Schwartz, Stephen G.
    Matsuura, Kazuki
    Tone, Stephan O.
    Arshinoff, Steve
    Ng, Jonathon Q.
    Meyer, Jay J.
    Liu, Wu
    Jacob, Soosan
    Packer, Mark
    Lutfiamida, Rifna
    Tahija, Sjakon
    Roux, Paul
    Malyugin, Boris
    Urrets-Zavalia, Julio A.
    Crim, Nicolas
    Esposito, Evangelina
    Daponte, Pablo
    Pellegrino, Fernando
    Graue-Hernandez, Enrique O.
    Jimenez-Corona, Aida
    Valdez-Garcia, Jorge E.
    Hernandez-Camarena, Julio C.
    Relhan, Nidhi
    Flynn, Harry W., Jr.
    Ravindran, Ravilla D.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Endophthalmitis Prophylaxis in Cataract Surgery: Overview of Current Practice Patterns Around the World2017In: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 23, no 4, p. 565-573Article, review/survey (Refereed)
    Abstract [en]

    Background: Acute-onset postoperative endophthalmitis after cataract surgery remains a rare but important cause of visual loss. There is no global consensus regarding the optimal strategies for prophylaxis of endophthalmitis and practices vary substantially around the world, especially with respect to the use of intracameral antibiotics. The European Society of Cataract & Refractive Surgeons in a randomized clinical trial (2007) reported an approximately 5-fold reduction in endophthalmitis rates associated with the use of intracameral cefuroxime. Despite this report, the use of intracameral antibiotics has not been universally adopted. Methods: Various endophthalmitis prophylaxis patterns around the world (including the United States, Canada, Australia/New Zealand, Japan, China, India, Indonesia, South Africa, Argentina, Russia, Sweden and Mexico) are compared. Each contributing author was asked to provide similar information, including endophthalmitis rates based on published studies, current practice patterns, and in some cases original survey data. Various methods were used to obtain this information, including literature reviews, expert commentary, and some new survey data not previously published. Results: Many different practice patterns were reported from around the world, specifically with respect to the use of intracameral antibiotics. Conclusion: There is no worldwide consensus regarding endophthalmitis prophylaxis with cataract surgery.

  • 82. Gudmundsdottir, Birna S.
    et al.
    Petursdottir, Dyrleif
    Asgrimsdottir, Gudrun M.
    Gottfredsdottir, Maria S.
    Hardarson, Sveinn H.
    Johannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kurkov, Sergey V.
    Jansook, Phatsawee
    Loftsson, Thorsteinn
    Stefansson, Einar
    gamma-Cyclodextrin Nanoparticle Eye Drops with Dorzolamide: Effect on Intraocular Pressure in Man2014In: Journal of Ocular Pharmacology and Therapeutics, ISSN 1080-7683, E-ISSN 1557-7732, Vol. 30, no 1, p. 35-41Article in journal (Refereed)
    Abstract [en]

    Purpose: To test a new drug delivery platform with dorzolamide γ-cyclodextrin (γCD) nanoparticle eye drops for intraocular pressure (IOP) control and safety and compare with Trusopt.® Methods: Self-aggregating γCD nanoparticle eye drops containing 3% dorzolamide were given once a day (QD) and compared with Trusopt given three times a day (TID) in a prospective randomized single masked crossover trial over 24 h. Seventeen subjects with IOP over 18 mmHg were recruited. IOP was measured with an Icare Tonometer Pro.® Results: There was no statistically significant difference in the IOP lowering effect of dorzolamide nanoparticle eye drops QD and Trusopt TID. At peak (4 h), the IOP reduction from baseline was 3.8±2.6 mmHg (18%, P<0.05) in the nanoparticle eye drop group and 3.1±3.7 mmHg in the Trusopt group (14%, P<0.05, P=0.97 between groups). At trough (24 h), the IOP reduction was 1.4±2.8 mmHg (6%, P>0.05) in nanoparticle eye drop group and 1.5±2.0 mmHg (7%, P>0.05) in the Trusopt group (P=0.23 between groups). Burning sensation measured on the visual analogue scale (1–100) was less from the nanoparticle eye drops (12±15) than from the Trusopt (37±30), (P=0.0038). Visual acuity and conjunctival hyperemia did not differ between the two groups. Conclusions: Dorzolamide cyclodextrin nanoparticle eye drops QD lower IOP and the effect seems comparable to Trusopt given TID. The nanoparticle eye drops are well tolerated and seem to have a better safety profile than Trusopt.

  • 83.
    Hadrevi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hellström, Fredrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Kieselbach, Thomas
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Malm, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Protein differences between human trapezius and vastus lateralis muscles determined with a proteomic approach2011In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 12, no 181, p. 11-Article in journal (Refereed)
    Abstract [en]

    Background: The trapezius muscle is a neck muscle that is susceptible to chronic pain conditions associated with repetitive tasks, commonly referred to as chronic work-related myalgia, hence making the trapezius a muscle of clinical interest. To provide a basis for further investigations of the proteomic traits of the trapezius muscle in disease, two-dimensional difference gel electrophoresis (2D-DIGE) was performed on the healthy trapezius using vastus lateralis as a reference. To obtain as much information as possible from the vast proteomic data set, both one-way ANOVA, with and without false discovery rate (FDR) correlation, and partial least square projection to latent structures with discriminant analysis (PLS-DA) were combined to compare the outcome of the analysis.

    Results: The trapezius and vastus lateralis showed significant differences in metabolic, contractile and regulatory proteins, with different results depending on choice of statistical approach and pre-processing technique. Using the standard method, FDR correlated one-way ANOVA, 42 protein spots differed significantly in abundance between the two muscles. Complementary analysis using immunohistochemistry and western blot confirmed the results from the 2D-DIGE analysis.

    Conclusions: The proteomic approach used in the present study combining 2D-DIGE and multivariate modelling provided a more comprehensive comparison of the protein profiles of the human trapezius and vastus lateralis muscle, than previously possible to obtain with immunohistochemistry or SDS-PAGE alone. Although 2D-DIGE has inherent limitations it is particularly useful to comprehensively screen for important structural and metabolic proteins, and appears to be a promising tool for future studies of patients suffering from chronic work related myalgia or other muscle diseases.

  • 84. Hallberg, Per
    et al.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Bäcklund, Tomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Clinical evaluation of applanation resonance tonometry: a comparison with Goldmann applanation tonometry.2007In: Journal of glaucoma, ISSN 1057-0829, E-ISSN 1536-481X, Vol. 16, no 1, p. 88-93Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this study was to calibrate and evaluate the precision of the new applanation resonance tonometry (ART) in a clinical study designed in accordance with the International Standard Organization's requirements. METHODS: This was a prospective, randomized, single-center study, where healthy volunteers and patients participated. A total of 153 eyes were divided into 3 groups with respect to their intraocular pressure (IOP) at screening: <16 mm Hg, 16 to 23 mm Hg, and >23 mm Hg. IOP was measured with Goldmann applanation tonometry (GAT) as reference method and by ART in both a biomicroscope (ARTBiom) and a handheld (ARTHand) setup with a 10-minutes pause between methods. The mean of 6 readings was regarded as one measurement value. RESULTS: Mean age of the subjects was 59 years (range 20 to 87 y). GAT showed a mean IOP of 20.0 mm Hg (range 8.5 to 43.5 mm Hg, n=153). The precision was 2.07 mm Hg for ARTBiom and 2.50 mm Hg for ARTHand, with a significant dependency for age as compared with GAT. Measurement order produced a decreasing IOP with a mean of 2.3 mm Hg between the first and last method. CONCLUSIONS: The precision obtained in both ARTBiom and ARTHand was within the limits set by the International Standard Organization standards for tonometers. The standardized procedure and the stability of the biomicroscope setup resulted in a slightly better precision as compared with the handheld setup. Despite a 10-minutes pause between measurements, the order was a significant factor, possibly because the patients were more apprehensive at the first measurement.

  • 85.
    Hallberg, Per
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Santala, Kenneth
    Koskela, Timo
    Lindahl, Olof A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Underestimation of intraocular pressure after photorefractive keratectomy - a biomechanical analysisArticle in journal (Refereed)
  • 86. Hallberg, Per
    et al.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Santala, Kenneth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Koskela, Timo
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindahl, Olof
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Underestimation of intraocular pressure after photorefractive keratectomy: a biomechanical analysis2006In: Med Biol Eng Comput, Vol. 44, p. 609-168Article in journal (Refereed)
    Abstract [en]

    Excimer laser surgery, to correct corneal refraction, induces changes in corneal thickness and curvature. Both factors can cause measurement errors when determining intraocular pressure (IOP). This study evaluates effects of photorefractive keratectomy (PRK) on IOP measurements, using Goldmann applanation tonometry (GAT) and Applanation resonance tonometry (ART), in an in vitro model. Six porcine eyes was enucleated and pressurised to a constant IOP=30 mmHg. After removal of the epithelium, the eyes were PRK-treated for a total of 25 dioptres. The measured IOP decreased 13.2 mmHg for GAT and 9.0 mmHg for ART. The total underestimation by GAT was larger than for ART, and a part of the ART underestimation (3.5 mmHg) was assigned to sensitivity to the change in corneal surface structure resulting from the removal of epithelium. The flat contact probe of GAT, as compared with the convex tip of ART, provided explanation for the difference in IOP measurement error after PRK.

  • 87.
    Hallberg, Per
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Bäcklund, Tomas
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Symmetric sensor for applanation resonance tonometry of the eye2006In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 44, no 1-2, p. 54-60Article in journal (Refereed)
    Abstract [en]

    Applanation resonance tonometry (ART) has been shown in a number of studies to be useful for measuring intraocular pressure (IOP). Data from in vitro laboratory bench testing, where the sensor was carefully centralised onto the cornea, has been very consistent with good precision in the determination of IOP. However, in a clinical study the unavoidable off-centre placement of the sensor against the cornea resulted in a reduced precision. The aim of this study was to evaluate a new design of the sensor with a symmetric sensor probe and a contact piece with a larger diameter. Two in vitro porcine eye experimental set-ups were used. One bench-based for examining position dependence and one biomicroscope-based set-up, simulating a clinical setting, for evaluating IOP(ART) precision at seven different pressure levels (1040 mmHg), set by connecting a saline column to the vitreous chamber. The reference IOP was recorded using a pressure transducer. There was no significant difference between four positions 1 mm off centre and the one centre position. The precision of the ART as compared with the reference pressure was +/- 1.03 mmHg (SD, n = 42). The design improvement has enhanced the precision of the ART in the biomicroscope set-up to be in parity with bench test results from a set-up using perfect positioning. This indicates that off-centre positioning was no longer a major contributor to the deviations in measured IOP. The precision was well within the limits set by ISO standard for eye tonometers. Therefore, a larger in vivo study on human eyes with the ART should be performed.

  • 88.
    Hallberg, Per
    et al.
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindahl, Olof A.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Bäcklund, Tomas
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Applanation resonance tonometry for intraocular pressure in humans2004In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 25, no 4, p. 1053-1065Article in journal (Refereed)
    Abstract [en]

    Glaucoma is a group of diseases associated with optic nerve damage and loss of visual field. The aetiology is not completely understood, but one of the major risk factors is elevated intraocular pressure (IOP). Reliable methods for measuring the IOP are therefore important. The aim of the study was to investigate the ability of the applanation resonance tonometry (ART) system, based on continuous force and area recording, to measure IOP in humans. Both the phase of initial indentation (IOPIndentation) and the phase when the sensor was removed (IOPRemoval) from the cornea were analysed. The Goldmann applanation tonometry (GAT) was used as reference method. The study included 24 healthy volunteers with normal IOP and 24 patients with elevated IOP. The correlation and standard deviation (SD) between IOPIndentation and IOPGAT was R = 0.92 (p < 0.001), SD = 3.6 mmHg, n = 104, and between IOPRemoval and IOPGAT R = 0.94 (p < 0.001), SD = 3.1 mmHg, n = 104. In conclusion, resonance sensor technology has made it possible to introduce a new multi-point method for measuring IOP, and the method is relevant for measuring IOP in humans. The study indicates that with further development towards elimination of position dependence, the ART has the potential to become a useful clinical instrument for IOP measurement.

  • 89.
    Hallberg, Per
    et al.
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Santala, Kenneth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindahl, Olof A
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Comparison of Goldmann applanation and applanation resonance tonometry in a biomicroscope-based in vitro porcine eye model2006In: J Med Eng Technol, ISSN 0309-1902, Vol. 30, no 6, p. 345-352Article in journal (Refereed)
  • 90.
    Harandi, Vahid M.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    A Muscle Perspective on the Pathophysiology of Amyotrophic Lateral Sclerosis: Differences between extraocular and limb muscles2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disorder. ALS has been traditionally believed to be primarily a motor neuron disease. However, accumulating data indicate that loss of contact between the axons and the muscle fibres occurs early; long before the death of motor neurons and that muscle fibres may initiate motor neuron degeneration. Thus, the view of ALS is changing focus from motor neurons alone to also include the muscle fibres and the neuromuscular junctions (NMJs). While skeletal muscles are affected in ALS, oculomotor disturbances are not dominant features of this disease and extraocular muscles (EOMs) are far less affected than limb muscles. Why oculomotor neurons and EOMs are capable to be more resistant in the pathogenetic process of ALS is still unknown.

    The overall goal of this thesis is to explore the pathophysiology of ALS from a muscle perspective and in particular study the expression and distribution of key neurotrophic factors (NTFs) and Wnt proteins in EOMs and limb muscles from ALS donors and from SOD1G93A transgenic mice. Comparisons were made with age-matched controls to distinguish between changes related to ALS and to ageing.

    Results: Brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4) were present in EOMs and limb muscles at both mRNA and protein levels in control mice. The mRNA levels of BDNF, NT-3 and NT-4 were significantly lower in EOMs than in limb muscles of early and/or late control mice, indicating an intrinsic difference in NTFs expression between EOMs and limb muscles. qRT-PCR analysis showed significantly upregulated mRNA levels of NT-3 and GDNF in EOMs but significantly downregulated mRNA levels of NT-4 in limb muscles from SOD1G93A transgenic mice at early stage. The NTFs were detected immunohistochemically in NMJs, nerve axons and muscle fibres. The expression of BDNF, GDNF and NT-4 on NMJs of limb muscles, but not of EOMs, was significantly decreased in terminal stage ALS animals as compared to the limb muscles of the age-matched controls. In contrast, NTFs expression in intramuscular nerve axons did not present significant changes in either muscle group of early or late ALS mice. NTFs, especially BDNF and NT-4 were upregulated in some small-sized muscle fibres in limb muscles of late stage ALS mice. All the four Wnt isoforms, Wnt1, Wnt3a, Wnt5a and Wnt7a were detected in most axon profiles in all human EOMs with ALS, whereas significantly fewer axon profiles were positive in the human limb muscles except for Wnt5a. Similar differential patterns were found in myofibres, except for Wnt7a, where its expression was elevated within sarcolemma of limb muscle fibres. β-catenin, a marker of the canonical Wnt pathway was activated in a subset of myofibres in the EOMs and limb muscle in all ALS patients. In the SOD1G93A mouse, all four Wnt isoforms were significantly decreased in the NMJs at the terminal stage compared to age matched controls.

    Conclusions: There were clear differences in NTF and Wnt expression patterns between EOM and limb muscle, suggesting that they may play a role in the distinct susceptibility of these two muscle groups to ALS. In particular, the early upregulation of GDNF and NT-3 in the EOMs might play a role in the preservation of the EOMs in ALS. Further studies are needed to determine whether these proteins and the pathways they control may be have a future potential as protecting agents for other muscles.

  • 91.
    Harandi, Vahid M
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Gaied, Aida RN
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Unchanged neurotrophic factors and their receptors correlate with sparing in extraocular muscles in amyotrophic lateral sclerosis2016In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, no 15, p. 6831-6842Article in journal (Refereed)
    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.

  • 92.
    Heijl, Anders
    et al.
    Skånes universitetssjukhus, Malmö.
    Alm, Albert
    Neurovetenskap, Ögon, Uppsala.
    Bengtsson, Boel
    Skånes universitetssjukhus, Malmö.
    Bergström, Anders
    Ögonkliniken Skånes universitetssjukhus, Malmö-Lund.
    Calissendorff, Berit
    S:t Eriks ögonsjukhus, Stockholm.
    Lindblom, Bertil
    Inst f neurovetenskaper, Sahlgrenska Akademin, Göteborgs universitet.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Riktlinjer för glaukomsjukvården2010Book (Refereed)
  • 93.
    Heijl, Anders
    et al.
    Department of Ophthalmology Skåne University Hospital Malmö, Malmö, Sweden .
    Alm, Albert
    Department of Ophthalmology, Academic Hospital, Uppsala, Sweden.
    Bengtsson, Boel
    Clinical Sciences Malmö, Department of Ophthalmology, Lund University, Lund, Sweden .
    Bergström, Anders
    Department of Ophthalmology, Skåne University Hospital Malmö-Lund, Sweden.
    Calissendorff, Berit
    St. Erik Eye Hospital, Stockholm, Sweden.
    Lindblom, Bertil
    Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The Glaucoma Guidelines of the Swedish Ophthalmological Society2012In: Acta ophthalmologica. Supplement, ISSN 1755-375X, no 251, p. 1-40Article in journal (Refereed)
  • 94.
    Heijl, Anders
    et al.
    Ogonkliniken, Skånes universitetssjukhus, Malmö.
    Alm, Albert
    Neurovetenskap, Ögon, Uppsala.
    Bengtsson, Boel
    Lund.
    Calissendorf, Berit
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eckerlund, Ingemar
    Öppenvinkelglaukom: diagnostik, uppföljning och behandling: En systematisk litteraturöversikt från SBU2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 19-20, p. 1311-1313Article in journal (Refereed)
    Abstract [sv]

    Sänkning av ögontrycket fördröjer synfältsförsämringen vid glaukom och minskar risken för utveckling av glaukom vid okulär hypertension.

    Det är oklart om laserbehandling eller kirurgi är bättre än behandling med ögondroppar.

    Modern, snabb synfältstestning har hög diagnostisk träffsäkerhet (sensitivitet och specificitet).

    Diagnostik baserad på expertbedömning av papillfoton har låg till måttligt hög diagnostisk träffsäkerhet.

    Moderna instrument baserade på datoriserad bildanalys har likvärdig diagnostisk träffsäkerhet.

    Särskild uppmärksamhet bör ägnas åt att säkerställa att gruppen glaukompatienter inte eftersätts i sjukvården.

    Behandlingen av glaukom och uppföljningen behöver individualiseras i ökad omfattning.

    Synfältsundersökning bör göras mer frekvent de första åren efter diagnos.

  • 95. Hellgren, Kerstin M.
    et al.
    Tornqvist, Kristina
    Jakobsson, Peter G.
    Lundgren, Pia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Carlsson, Birgitta
    Kallen, Karin
    Serenius, Fredrik
    Hellstrom, Ann
    Holmstrom, Gerd
    Ophthalmologic Outcome of Extremely Preterm Infants at 6.5 Years of Age Extremely Preterm Infants in Sweden Study (EXPRESS)2016In: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 134, no 5, p. 555-562Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE This follow-up study of extremely preterm (EPT) children (<27 weeks' gestational age [GA] at birth) revealed major eye and visual problems in 37.9%(147 of 388) of all EPT infants and in 55.4%(67 of 121) of the most immature subgroups at 6.5 years of age. These major eye and visual problems were strongly associated with treatment-requiring retinopathy of prematurity (ROP). OBJECTIVES To investigate the ophthalmologic outcome of a national cohort of EPT children at 6.5 years of age and to evaluate the impact of prematurity and ROP. DESIGN, SETTING, AND PARTICIPANTS All surviving EPT children born in Sweden between April 1, 2004, and March 31, 2007, were included and compared with a matched term control group, as part of a prospective national follow-up study. MAIN OUTCOMES AND MEASURES Visual acuity, refraction in cycloplegia, and manifest strabismus were evaluated and compared with GA at birth and with treatment-requiring ROP. RESULTS The study cohort comprised 486 participants. The mean (SD) GA of the children who were included was 25 (1) weeks, and 45.7%(222 of 486) were female. At a median age of 6.6 years, 89.3%(434 of 486) of eligible EPT children were assessed and compared with 300 control group children. In the EPT group, 2.1%(9 of 434) were blind, 4.8%(21 of 434) were visually impaired according to the World Health Organization criteria, and 8.8% (38 of 434) were visually impaired according to the study criteria. Strabismus was found in 17.4% (68 of 390) and refractive errors in 29.7%(115 of 387) of the EPT children compared with 0% (0 of 299) and 5.9% (17 of 289), respectively, of the control children (P<.001). Altogether at 6.5 years of age, 37.9%(147 of 388) of the EPT children had some ophthalmologic abnormality compared with 6.2%(18 of 290) of the matched control group (95% CI of the difference, 26.1%-37.2%). When treatment-requiring ROP was adjusted for, no significant association between GA and visual impairment could be detected. For refractive errors, the association with GA remained after adjustment for treatment-requiring ROP (odds ratio, 0.72; 95% CI, 0.58-0.91 for each 1-week increment). CONCLUSIONS AND RELEVANCE In a Swedish national cohort of EPT children at 6.5 years of age, major eye and visual problems were frequently found. Treatment-requiring ROP was a stronger impact factor than GA on visual impairment and strabismus, but not on refractive errors, as a whole. In modern neonatal intensive care settings, ophthalmologic problems continue to account for a high proportion of long-term sequelae of prematurity.

  • 96. Hellstrom, Ann
    et al.
    Kallen, Karin
    Carlsson, Birgitta
    Holmstrom, Gerd
    Jakobsson, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lundgren, Pia
    Serenius, Fredrik
    Stjernqvist, Karin
    Tornqvist, Kristina
    Hellgren, Kerstin
    Extreme prematurity, treated retinopathy, bronchopulmonary dysplasia and cerebral palsy are significant risk factors for ophthalmological abnormalities at 6.5 years of age2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 5, p. 811-821Article in journal (Refereed)
    Abstract [en]

    Aim: This study evaluated the contributions of various prenatal and postnatal predictive factors to a documented high prevalence of ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm. Methods: We carried out a prospective population-based study of all children born in Sweden at a gestational age of 22 + 0 to 26 + 6 weeks based on the Extremely Preterm Infants in Sweden Study. The main outcome measures were a combined score of visual impairment, refractive errors and strabismus at 6.5 years of age. Models of univariate and multivariable regression were used to analyse potential prenatal and postnatal predictive factors at different clinically relevant time-points from one minute after birth to 30 months. Results: We focused on 399 known extremely preterm survivors and compared them to 300 full-term controls. Significant antecedents for ophthalmological abnormalities included prematurity per se, retinopathy of prematurity that required treatment, severe bronchopulmonary dysplasia and cerebral palsy. Severe intraventricular haemorrhage was no longer a significant risk factor when we adjusted it for the 30-month cognitive and neuromotor development outcomes. Conclusion: This time-course risk analysis model showed a changing panorama of significant risk factors for ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm.

  • 97. Herbst, Kristina
    et al.
    Sander, Birgit
    Lund-Andersen, Henrik
    Broendsted, Adam Elias
    Kessel, Line
    Hansen, Michael Stormly
    Kawasaki, Aki
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intrinsically photosensitive retinal ganglion cell function in relation to age: A pupillometric study in humans with special reference to the age-related optic properties of the lens.2012In: BMC Ophthalmology, ISSN 1471-2415, E-ISSN 1471-2415, Vol. 12, no 4Article in journal (Refereed)
    Abstract [en]

    Background: The activity of melanopsin containing intrinsically photosensitive ganglion retinal cells (ipRGC) can be assessed by a means of pupil responses to bright blue (appr.480 nm) light. Due to age related factors in the eye, particularly, structural changes of the lens, less light reaches retina. The aim of this study was to examine how age and in vivo measured lens transmission of blue light might affect pupil light responses, in particular, mediated by the ipRGC.

    Methods: Consensual pupil responses were explored in 44 healthy subjects aged between 26 and 68 years. A pupil response was recorded to a continuous 20 s light stimulus of 660 nm (red) or 470 nm (blue) both at 300 cd/m2 intensity (14.9 and 14.8 log photons/cm2/s, respectively). Additional recordings were performed using four 470 nm stimulus intensities of 3, 30, 100 and 300 cd/m2. The baseline pupil size was measured in darkness and results were adjusted for the baseline pupil and gender. The main outcome parameters were maximal and sustained pupil contraction amplitudes and the postillumination response assessed as area under the curve (AUC) over two time-windows: early (0–10 s after light termination) and late (10–30 s after light termination). Lens transmission was measured with an ocular fluorometer.

    Results: The sustained pupil contraction and the early poststimulus AUC correlated positively with age (p = 0.02, p = 0.0014, respectively) for the blue light stimulus condition only.

    The maximal pupil contraction amplitude did not correlate to age either for bright blue or red light stimulus conditions.

    Lens transmission decreased linearly with age (p < 0.0001). The pupil response was stable or increased with decreasing transmission, though only significantly for the early poststimulus AUC to 300 cd/m2 light (p = 0.02).

    Conclusions: Age did not reduce, but rather enhance pupil responses mediated by ipRGC. The age related decrease of blue light transmission led to similar results, however, the effect of age was greater on these pupil responses than that of the lens transmission. Thus there must be other age related factors such as lens scatter and/or adaptive processes influencing the ipRGC mediated pupil response enhancement observed with advancing age.

  • 98.
    Hittenkofer, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Extraocular muscles in R350P desminopathy2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 99.
    Holmgren, Gösta
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lundgren, Hans-Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sandgren, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Impact of homozygosity for an amyloidogenic transthyretin mutation on phenotype and long term outcome.2005In: Journal of Medical Genetics, ISSN 1468-6244, Vol. 42, no 12, p. 953-6Article in journal (Refereed)
  • 100. Holmstrom, Gerd
    et al.
    Hellstrom, Ann
    Jakobsson, Peter
    Lundgren, Pia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Tornqvist, Kristina
    Wallin, Agneta
    Five years of treatment for retinopathy of prematurity in Sweden: results from SWEDROP, a national quality register2016In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 100, no 12, p. 1656-1661Article in journal (Refereed)
    Abstract [en]

    Background/aims Retinopathy of prematurity (ROP) is a sight-threatening disease, requiring efficient screening and treatment. The present study aims to describe various aspects on treatment for ROP in Sweden.

    Methods Data on treatment for ROP in infants born in 2008-2012 were extracted from Swedish national register for retinopathy of prematurity, a web-based national register.

    Results During 2008-2012, 3488 infants with a gestational age (GA) at birth of <31 weeks had been screened for ROP in Sweden. Altogether, 30.3% (1057/3488) of the infants developed ROP and 5.2% (181/3488) were treated. Type 1 ROP was found in at least one eye in 83.2% (149/179) of the treated infants. One third of the eyes (32.2% right, 29.9% left eyes) were treated more than once. Laser was the only treatment in 90% of the eyes. Mean number of laser spots at first laser session was 1177 and 1386 in right and left eyes, respectively. Number of laser spots correlated negatively with GA at birth (p=0.01). There was no change in frequency of treatment or number of laser spots during the 5-year period. Anti-vascular endothelial growth factor injections were performed in 28 eyes, encircling band was used in five eyes and vitrectomies were performed in seven eyes. Twenty-six retinal surgeons performed 9.4 (range 1-37) treatment sessions in the 181 infants.

    Conclusions The present study reveals similar incidences of ROP and frequencies of treatment during the 5-year study period. Many surgeons were involved in treatment of a rather limited number of infants. The results call for national discussions on organisation of ROP treatment.

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