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Catherine Cheng, Xiaohua Gong; Disruption Of Epithelial Cells In Ephrin-A5 Knockout Lenses. Invest. Ophthalmol. Vis. Sci. 2011;52(14):810.
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To investigate the mechanism for how disrupted of Eph-ephirn signaling leads to age-related cataracts in humans and mice, and to study the roles of Eph-ephrin in the lens during development by using ephrin-A5 knockout (-/-) mice.
Lens phenotypes of ephrin-A5(-/-) mice were examined using histology, and confocal images of GFP-positive lens epithelial and fiber cells were collected. Cell-cell junctions, cell adhesions and cytoskeletal structures were examined by immunohistochemistry. Lens signaling and structure proteins were analyzed by biochemical methods.
Ephrin-A5(-/-) mice develop variable cataract phenotypes with incomplete penetrance. Morphological data reveal aberrant or mislocalized epithelial cells and selectively disorganized fiber cells in ephrin-A5(-/-) lenses. Images of GFP-positive ephrin-A5(-/-) lenses show central epithelial cells with irregular shape and/or size and small areas of disordered fiber cells. Three-dimensional reconstruction show epithelial cells dipped into the anterior suture in some ephrin-A5(-/-) lenses. Immunostaining reveal that ephrin-A5 proteins are highly expressed at the lateral surfaces of lens epithelial cells and the distribution of N-cadherin and beta-catenin proteins are disrupted in ephrin-A5(-/-) epithelial cells.
The loss of ephrin-A5 causes obvious changes in lens epithelial cells, indicating that ephrin-A5 signaling is essential for maintaining the morphology, polarity and communication of epithelial cells. These changes in the epithelial cells are likely to be early events that lead to cataracts in ephrin-A5(-/-) lenses. Thus, variable cataract formation in ephrin-A5(-/-) lenses is at least in part due to interactions between altered epithelial cells and disorganized underlying fiber cells.
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