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Distribution of laminins in the developing human eye
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
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2006 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, Vol. 47, no 3, 777-785 p.Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
Association for Research in Vision and Ophthalmology , 2006. Vol. 47, no 3, 777-785 p.
Keyword [en]
Basement Membrane/embryology/metabolism, Cornea/*embryology/metabolism, Eye Proteins/*metabolism, Fetal Development, Fluorescent Antibody Technique; Indirect, Gestational Age, Humans, Laminin/*metabolism, Lens; Crystalline/*embryology/metabolism, Microscopy; Fluorescence, Morphogenesis, Protein Isoforms/metabolism, Retina/*embryology
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URN: urn:nbn:se:umu:diva-12671DOI: 10.1167/iovs.05-0367PubMedID: 16505007OAI: diva2:152342
Available from: 2007-12-27 Created: 2007-12-27 Last updated: 2013-12-12Bibliographically 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: 2011-04-08Bibliographically approved

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