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 β1 (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 β1 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.
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 β1 (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 humancorneal disease keratoconus. The phenotype did not develop when Itgb1 was deleted after complete corneal maturation. CONCLUSIONS: Loss of integrin β1 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.
Authors: Sina Sharifi; Hannah Sharifi; Ali Akbari; Darrell Koza; Claes H Dohlman; Eleftherios I Paschalis; James Chodosh Journal: ACS Appl Bio Mater Date: 2021-09-21
Authors: Ying Liu; Hu Huang; Guoying Sun; Saeed Alwadani; Richard D Semba; Gerard A Lutty; Samuel Yiu; Deepak P Edward Journal: Curr Eye Res Date: 2016-07-21 Impact factor: 2.424
Authors: Sina Sharifi; Mohammad Mirazul Islam; Hannah Sharifi; Rakibul Islam; Per H Nilsson; Claes H Dohlman; Tom Eirik Mollnes; Eleftherios I Paschalis; James Chodosh Journal: Transl Vis Sci Technol Date: 2020-12-23 Impact factor: 3.283
Authors: Chloe M Stanton; Amy S Findlay; Camilla Drake; Mohammad Z Mustafa; Philippe Gautier; Lisa McKie; Ian J Jackson; Veronique Vitart Journal: Dis Model Mech Date: 2021-09-22 Impact factor: 5.758