Peer Review #2 of "Polarity and epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy (v0.1)"

Under physiological conditions, retinal pigment epithelium (RPE) is a cellular monolayer composed of mitotically quiescent cells.Tight junctions and adherens junctions maintain the polarity of RPE cells, and are required for cellular functions.In proliferative vitreoretinopathy (PVR), upon retinal tear, RPE cells lose cell-cell contact, undergo epithelial-mesenchymal transition (EMT), and ultimately transform into myofibroblasts, leading to the formation of fibrocellular membranes on both surfaces of the detached retina and on the posterior hyaloids, which causes tractional retinal detachment.In PVR, RPE cells are crucial contributors, and multiple signaling pathways, including SMADdependent pathway, Rho pathway, MAPK pathways, Jagged/Notch pathway, and Wnt/βcatenin pathway, are activated.These pathways mediate the EMT of RPE cells, which play a key role in the pathogenesis of PVR.This review summarizes the current body of knowledge on the polarized phenotype of RPE, the role of cell-cell contact, and the molecular mechanisms underlying the RPE EMT in PVR, emphasizing key insights into potential approaches to prevent PVR.