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Mallika Pathania, Vladimir N. Simirskii, Melinda K. Duncan; The Function Of β 1-integrin In Lens Epithelial Cells Changes During Development. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2789.
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β1-integrins are heterodimeric cell surface receptors that participate in cell-extracellular matrix interactions and cell-cell signaling. Deletion of the β1-integrin subunit from the lens epithelium results in EMT and apoptosis of lens epithelial cells. These mice are anopthalmic as adults. This shows that β1-integrin is required for maintenance of lens epithelial phenotype and for survival of lens epithelial cells after lens development. Additionally β1- integrin is known to play a role in the development of various tissues such as skin and pancreas. In the lens, β1-integrin is detectable at all stages of lens development suggesting its role in development of lens as well. This work tests the role of β1-integrin in early lens morphogenesis.
Mice were created homozygous for the β1-integrin floxed allele and heterozygous for Le-Cre transgene which is expressed in cells of the surface ectoderm starting at lens placode stage. Loss of β1-integrin gene expression was determined by PCR and immunostaining. Lens morphology was assessed by histological analysis. Expression of lens epithelial and fiber cell markers as well as basement membrane components was studied by immunolocalization.
β1-integrin protein is lost at the lens vesicle stage (10.5 dpc) in homozygous β1- integrin floxed/LE-Cre (β1-LE) mice. β1-LE mice are anopthalmic as adults, however, in contrast to lenses which lose β1-integrin protein at 12.5 dpc, the lens epithelium of β1-LE mice does not undergo EMT as assessed by immunostaining for αSMA. Instead, the entire lens epithelium undergoes robust fiber cell differentiation by 13.5 dpc as measured by cell morphology and the expression of β-crystallin, γ-crystallin and aquaporin 0. Further, these lenses have disorganized lens capsules by 12.5 dpc leading to its near complete dissolution by 14.5 dpc.
Our data suggests that β1-integrin prevents inappropriate differentiation of the lens epithelium into fibers shortly after lens formation while later in development, β1-integrin seems to block lens epithelial cells from entering the EMT pathway. Further, early in lens development β1-integrins are essential for maintenance of lens capsule while lens capsule defects are not observed in lenses which lose β1-integrin after lens formation. Overall these data demonstrate that β1-integrin function changes during lens development.
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