Pigment Epithelia of the Eye: Cell-Type Conversion in Regeneration and Disease

Pigment epithelial cells (PECs) of the retina (RPE), ciliary body, and iris (IPE) are capable of altering their phenotype. The main pathway of phenotypic switching of eye PECs in vertebrates and humans in vivo and/or in vitro is neural/retinal. Besides, cells of amphibian IPE give rise to the lens and its derivatives, while mammalian and human RPE can be converted along the mesenchymal pathway. The PECs' capability of conversion in vivo underlies the lens and retinal regeneration in lower vertebrates and retinal diseases such as proliferative vitreoretinopathy and fibrosis in mammals and humans. The present review considers these processes studied in vitro and in vivo in animal models and in humans. The molecular basis of conversion strategies in PECs is elucidated. Being predetermined onto- and phylogenetically, it includes a species-specific molecular context, differential expression of transcription factors, signaling pathways, and epigenomic changes. The accumulated knowledge regarding the mechanisms of PECs phenotypic switching allows the development of approaches to specified conversion for many purposes: obtaining cells for transplantation, creating conditions to stimulate natural regeneration of the retina and the lens, blocking undesirable conversions associated with eye pathology, and finding molecular markers of pathology to be targets of therapy.