Abstract
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.
Highlights
The pigment epithelial cells (PECs) in the vertebrate eye are considered both a po
The role of transcription factors (TFs) in the specification of neural retina (NR) progenitors during regeneration in frogs was studied using the example of the rax gene, whose expression is up-regulated in Retinal Pigment Epithelial (RPE)-derived neuroblasts, while the rax knock-down impairs retinal cell types in retina regeneration in tadpoles [172,173]
Specifics of this response of mammalian cell-type conversions in animals, it is evident that these ones involve changes in the RPE cells are manifested as the loss of polarity, destruction of cell–cell junctional com expression of functionally significant genes controlled by specific TFs, regulatory signaling plexes, including adhering junctions and tight junctions, and detachment from th systems, and epigenetic factors
Summary
The pigment epithelial cells (PECs) in the vertebrate eye are considered both a po. 1. The interest in the phenomenon of cell-type conversion and the further development of knowledge about it are relevant for many reasons These are required to understand to what extent the mechanisms of this process are common and what regulatory mechanisms provide similarities and differences between the positive (regeneration) and negative (pathology) results of transdifferentiation of the same tissue in different vertebrates. This knowledge is of practical value to be potentially applied in regenerative medicine for the purpose of protecting eye tissues, in particular the retina, from degenerative disorders and creating conditions for regeneration. The identification of key molecules and links in the regulatory mechanisms of cell-type conversion identifies the targets and factors influencing them, which allows prevention and treatment of pathology
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