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Publication : Integrin β1 is necessary for the maintenance of corneal structural integrity.

First Author  Parapuram SK Year  2011
Journal  Invest Ophthalmol Vis Sci Volume  52
Issue  11 Pages  7799-806
PubMed ID  21873663 Mgi Jnum  J:189378
Mgi Id  MGI:5445454 Doi  10.1167/iovs.10-6945
Citation  Parapuram SK, et al. (2011) Integrin beta1 is necessary for the maintenance of corneal structural integrity. Invest Ophthalmol Vis Sci 52(11):7799-806
abstractText  PURPOSE: The precise role of a normal keratocyte in maintaining corneal structural integrity is unclear; it is generally considered to remain quiescent at the end of cell division. Given that integrins are essential for cell/extracellular matrix interactions, the authors tested the hypothesis that integrin expression by keratocytes is essential for corneal structure and function. METHODS: Using a tamoxifen-dependent cre recombinase expressed under the control of a fibroblast-specific promoter/enhancer, the authors conditionally deleted the integrin beta1 (Itgb1) gene in mouse keratocytes during the postnatal matrix maturation phase of the cornea. The effects of this deletion were monitored histologically and by macroscopic observation of the cornea. RESULTS: The resultant cornea shows an initial thinning of the stroma, reduced space between collagen fibrils, loss of epithelial layers and subsequent edema, thickening of Descemet's membrane, and degenerative changes in the endothelial cell layer, with eventual scarring. These pathologic changes have some similarities to human corneal disease keratoconus. The phenotype did not develop when Itgb1 was deleted after complete corneal maturation. CONCLUSIONS: Loss of integrin beta1 expression in keratocytes during the phase of stromal maturation results in corneal thinning and edema. Keratocyte-ECM interaction is essential for matrix maturation and thus in the maintenance of corneal structural integrity. This model has relevance in understanding corneal diseases such as keratoconus.
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