Purpose.: Molecular mechanisms that initiate epithelial-mesenchymal transition (EMT) involved in ocular fibrotic complications remain elusive. Studies were conducted to examine the role of cell-cell contact in regulating EMT and proliferation of retinal pigment epithelial (RPE) cells. Methods.: Porcine RPE cells were isolated as sheets and cultured in vitro on lens capsules. Cell morphology was examined by microscopy. Western blot analysis and immunostaining were used to follow protein expression. Cell proliferation and RPE function were assessed by BrdU incorporation and phagocytosis assay, respectively. Results.: RPE cells in the center of each sheet maintained cell-cell contacts and retained a differentiated phenotype. Disruption of cadherin function in these cells resulted in the loss of cell-cell contact and the 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, which was accompanied by a switch in cadherin expression from P-cadherin to N-cadherin. Although TGF-β is thought to be a classic inducer of EMT, it was unable to initiate EMT in RPE cells maintaining cell-cell contact. However, change to α-SMA–positive myofibroblasts was induced by TGF-β in cells that had already undergone EMT. Conclusions.: EMT and the onset of proliferation in RPE cells is initiated by loss of cell-cell contact. TGF-β cannot initiate EMT or the 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.

The purpose of the present study was to evaluate the intraretinal migration of the retinal pigment epithelium (RPE) cells in age-related macular degeneration (AMD) using polarimetry. We evaluated 155 eyes at various AMD stages. Depolarized light images were computed using a polarization-sensitive scanning laser ophthalmoscope (PS-SLO), and the degree of polarization uniformity was calculated using polarization-sensitive optical coherence tomography (OCT). Each polarimetry image was compared with the corresponding autofluorescence (AF) images at 488 nm (SW-AF) and at 787 nm (NIR-AF). Intraretinal RPE migration was defined by the presence of depolarization at intraretinal hyperreflective foci on PS-SLO and PS-OCT images, and by the presence of hyper-AF on both NIR-AF and SW-AF images. RPE migration was detected in 52 of 155 eyes (33.5%) and was observed in drusenoid pigment epithelial detachment (PED) and serous PED with significantly higher frequencies than in other groups (P = 0.015). The volume of the migrated RPE cluster in serous PED was significantly correlated with the volume of the PED (R² = 0.26; P = 0.011). Overall, our results showed that intraretinal RPE migrations occurred in various AMD stages, and that they occurred more commonly in eyes with serous and drusenoid PED.