Epithelial-Mesenchymal Transition: Molecular Mechanisms of Retinal Pigment Epithelial Cell Activation

Activated cells of human retinal pigment epithelium (RPE) are the main effector cells in the process of fibrosis, the main pathological manifestation of proliferative vitreoretinal diseases of the retina. In the case of rhegmatogenous retinal detachment, resting RPE cells are activated and gain the phenotype of fibroblast- and myofibroblast-like cells, which intensively proliferate and migrate to the epiretinal space, where they create a favorable microenvironment for the development of fibrosis and/or contribute to its progression. The increased contractility of cells eventually leads to traction retinal detachment and loss of visual acuity. To date, various cellular signals have been identified that promote the activation of RPE cells, such as transforming growth factor beta, fibroblast growth factor-2, platelet-derived growth factor, mitogen-activated protein kinase, Smads, and NF-kappa B. Therefore, studying the role of these factors and signaling pathways in the activation of RPE cells will contribute to the development of therapeutic strategies and provide new opportunities for the treatment of retinal diseases. The review summarizes current knowledge about stimulating factors and signaling pathways in regulating cellular and molecular mechanisms of dedifferentiation and epithelial-mesenchymal transition (EMT) of RPE cells, which were largely determined by studying the effects of various signaling molecules in vitro. In addition, the role of microRNAs in regulating the TGF-beta signaling pathway and EMT is discussed, and promising therapeutic agents are considered.