Retinal pigment epithelial cells as a therapeutic tool and target against retinopathies

•RPE epithelial barrier features play a key part in rethinopathies.•Adult human RPE cultured cells can express neuronal markers.•HRPE cells customized for tracking processes related to retinal diseases.•SVCT2, GLUTs, MRPs, OR51E2 are targets in cell-based therapies and drug delivery.•RARβ is a topic for renewal of retinal dopaminergic precursors in RPE cells. Retinal pigment epithelium (RPE) is a cell monolayer essential for photoreceptor function and forming the blood–retinal barrier. RPE and retinal neurons share the same origin and a polarized cytoarchitecture. Several factors determine the phagocytosis and permeability of RPE, influencing photoreceptor renewal and drug delivery, efficacy and toxicity. Adult human RPE expresses neuronal markers in vitro, indicating a potential transdifferentiation. Degeneration of the RPE leads to death of photoreceptors and retinal neurons, resulting in the vision loss of retinopathy. Here, we suggest tools for cell engineering to discover new ways for activating the endogenous regeneration of barrier functions and/or of the retinal precursors in RPE cells.