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S. Tamiya, L. Liu, D. C. Dean, H. J. Kaplan; Loss of Cell-Cell Contact Initiates Epithelial-Mesenchymal Transition and Proliferation of Retinal Pigment Epithelial (RPE) Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2489.
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Epithelial-to-mesenchymal transition (EMT) and proliferation of RPE cells has been implicated to play a role in the development of proliferative vitreoretinopathy (PVR). However, molecular mechanisms that initiate EMT remain elusive. Studies were conducted to examine the role of cell-cell contact in regulating EMT and proliferation of RPE cells.
Porcine RPE cells were isolated as sheets and cultured in vitro on lens capsule. Cell morphology was examined by light and electron microscopy. Western blotting and immunostaining were used to follow protein expression. Cell proliferation was assessed by BrdU incorporation.
RPE cells in the center of the sheet maintained cell-cell contact and retained a differentiated phenotype. Disruption of cadherin function in these cells resulted in loss of cell-cell contact and concomitant induction of mesenchymal marker protein expression and cell proliferation. RPE cells at the edge of the sheet migrated away from the sheet, underwent EMT and initiated proliferation. While TGF-beta is thought to be a classic inducer of EMT, it was unable to initiate EMT in RPE cells maintaining cell-cell contact. However, it induced a change to alpha-smooth muscle actin positive myofibroblasts in cells that had already undergone EMT.
EMT and the onset of proliferation in RPE cells is initiated by loss of cell-cell contact. TGF-beta cannot initiate EMT or proliferation of RPE cells maintaining cell-cell contact but appears to play an important secondary role downstream of EMT in inducing transition to a myofibroblast phenotype - a phenotype linked to the development of fibrotic complications.
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