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Laminins in normal, keratoconus, bullous keratopathy and scarred human corneas
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
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2007 (English)In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 127, no 6, 657-667 p.Article in journal (Refereed) Published
Abstract [en]

The laminin composition (LMalpha1-alpha5, beta1-beta3, gamma1 and gamma2 chains) of normal corneas and corneal buttons from keratoconus, bullous keratopathy (BKP), Fuchs' dystrophy + BKP, Fuchs' dystrophy without BKP and scar after deep lamellar keratoplasty (DLKP) was investigated with immunohistochemistry. The epithelial basement membranes (BMs) of both normal and diseased corneas contained LMalpha3, alpha5, beta1, beta3, gamma1 and gamma2 chains. The epithelial BM morphology was altered in the different diseases. Scarring was associated with irregular BM and ectopic stromal localization of different laminin chains. The Descemet's membrane (DM) contained LMalpha5, beta1 and gamma1 chains in all cases and additionally LMbeta3 and gamma2 chains in the majority of keratoconus corneas. The interface in the DLKP cornea had patches of LMalpha3, alpha4, alpha5, beta1 and beta2 chains, and an extra BM-like structure under the Bowman's membrane. These results suggest that laminin chains participate in the process of corneal scarring and in the pathogenesis of some corneal diseases. The novel finding of LMalpha3, beta3 and gamma2 in the DM of keratoconus buttons indicates that this membrane is also involved in the disease and that some cases of keratoconus may have a congenital origin, without normal downregulation of the LMbeta3 chain.

Place, publisher, year, edition, pages
2007. Vol. 127, no 6, 657-667 p.
Keyword [en]
Laminin - Cornea - Human - Keratoconus - Basement membrane
URN: urn:nbn:se:umu:diva-3717DOI: 10.1007/s00418-007-0288-4PubMedID: 17492460Local ID: 744OAI: diva2:142543
Available from: 2008-12-19 Created: 2008-12-19 Last updated: 2011-08-26Bibliographically approved
In thesis
1. Laminins and alpha11 integrin in the human eye: importance in development and disease
Open this publication in new window or tab >>Laminins and alpha11 integrin in the human eye: importance in development and disease
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The extracellular matrix (ECM) offers a protective shelter for cells and provides signaling paths important for cell to cell communication. ECM consists of basement membranes (BM) and interstitial matrix. BMs provide mechanical support for parenchymal cells, influence cell proliferation, survival, migration and differentiation. They are also important for tissue integrity. Laminins (LM) are the major non-collagenous component of BMs. Cell-ECM interactions, mediated by receptors, are indispensable during embryonic development, wound healing, remodeling and homeostasis of tissues. The integrins are the major cell-adhesion receptors. The expression of alpha11 integrin chain in the cornea is of great interest, as it is part of the alpha11beta1 integrin receptor for collagen type I, the predominant component of the corneal stroma.

The aims were to thoroughly characterize the ECM in the developing and adult human eye, with particular focus on the cornea, LM and alpha11 integrin chains, and to examine alpha11 integrin chain in an animal model of corneal wound healing and remodeling. Human fetal eyes, 9-20 weeks of gestation (wg), and adult human corneas with different diagnosis were treated for immunohistochemistry with specific antibodies against LM and alpha11 integrin chains. Normal and knockout (ko) mice were treated with laser surgery to create a deep wound in the corneal stroma. The wound healing process was followed at different time points. The cellular source of alpha11 integrin chain was studied in cell cultures.

In the fetal eyes, the BM of the corneal epithelium, the Descemet’s membrane (DM) and the Bruch’s membrane each had their specific combinations of LM chains and time line of development, whereas the lens capsule and the internal limiting membrane showed constant LM chain patterns.

The epithelial BMs of normal and diseased adult corneas contained similar LM chains. The normal morphology of the epithelial BM was altered in the different diseases, particularly when scarring was present. In the scarred keratoconus corneas there were excessive LM chains. The majority of keratoconus corneas also expressed extra LM chains in the DM.

At 10-17 wg alpha11 integrin chain was present in the human corneal stroma, especially in the anterior portion, but it was scarce at 20 wg, in normal adult corneas and in Fuchs’ endothelial dystrophy. In contrast, it was increased in the anterior portion of the stroma in keratoconus corneas with scarring. Alpha11 integrin ko mice had a defective healing with subsequent thinner corneas. Alpha11 integrin expression correlated to the presence of alpha-smooth muscle actin in vivo as well as in vitro.

The distinct spatial and temporal patterns of distribution for alpha11 integrin and each of the LM chains suggest that they play an important role in human ocular differentiation. The selectively affected LM composition and the novel expression of alpha11 integrin chain in scarred keratoconus corneas as well as the pathologic healing in ko mice, indicate that alpha11 integrin and LM chains also play an important role in the process of corneal healing, remodeling and scarring and might participate in the pathogenesis of corneal disease. This knowledge is of practical importance for future topical therapeutic agents capable of modulating the corneal wound healing processes.

Place, publisher, year, edition, pages
Umeå: Oftalmiatrik, 2008. 53 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1229
basement membranes, extracellular matrix, laminin, integrin, cornea, development, keratoconus, wound healing, remodeling, immunohistochemistry
National Category
urn:nbn:se:umu:diva-1950 (URN)978-91-7264-696-4 (ISBN)
Public defence
2009-01-23, Betula, Bottenvåningen, Norrlands UniversitetsSjukhus, Umeå, 09:00 (English)
Available from: 2008-12-19 Created: 2008-12-19 Last updated: 2016-10-27Bibliographically approved

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Byström, BeritLindén, ChristinaPedrosa-Domellöf, Fatima
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