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F. Mamuya, Y. Wang, V. N. Simirskiy, M. K. Duncan; The Role of V-integrin in Lens Epithelial-Mesenchymal Transition. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2633.
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Integrins are hypothesized to plays significant role in Posterior Capsular Opacification (PCO). However, the identity and function of the integrins participating in this process is poorly understood. Our previous results showed that removal of lens fiber cells from mouse lenses results in robust lens epithelial cell (LEC) multilayering coincident with the upregulation of α-smooth muscle actin (αSMA) as well as the β1, β8, β5, αV and α5 integrin subunits within 48hrs post surgery. While the upregulation of β1-integrin and αSMA in post surgical lenses is well known, our results indicated that vast majority of the upregulated integrin subunits were capable of forming αV integrins. The aim of this study is to test the hypothesis that αV integrin is important for the lens epithelial-mesenchymal transition (EMT) that occurs after lens surgery/injury.
Mice harboring a floxed αV-integrin allele were mated with mice expressing CRE in all lens cells (MLR10). The resulting mice were characterized phenotypically while PCR and immunofluorescence was used to confirm the deletion of αV integrin in the lens. At three months of age, fiber cells were surgically removed from mutant and wildtype control lenses and the extent of EMT was measured 48 hours later by immunofluorescent detection of EMT markers.
Immunofluorescence analysis showed a near total loss of the αV integrin protein from putative null lenses although PCR indicated that the deletion was not 100%. Lenses lacking αV-integrin subunits are transparent but weigh significantly more than wild type lenses. Electron microscopy analysis revealed slight irregularities in αV integrin knockout’s fiber cells ball-and-socket interdigitations. When challenged with surgery/injury, LECs expressing αV-integrin subunits showed increase in LECs multilayering with upregulation of αSMA 48hrs post surgery. In contrast, LECs lacking αV-integrin subunits showed no increase in LECs multilayering with little to no upregulation of αSMA 48hrs post surgery.
These results suggest that αV-integrin is involved in the epithelial-mesenchymal transition mechanism that leads to posterior capsular opacification.
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