Reprogramming of Differentiated Mammalian and Human Retinal Pigment Epithelium: Current Achievements and Prospects
Impairment of the homeostatic and functional integrity of the retina and retinal pigment epithelium (RPE) is the main reason of a number of degenerative diseases of the human eye, accompanied by loss of vision. Despite the significant progress made over the past decades in the development of new methods of treatment for this pathology, a number of complications remain when using surgical methods of vision correction and so far insurmountable limitations in the use of modern approaches, such as gene therapy and genetic engineering. One of the promising approaches to the treatment of degenerative diseases of the retina may be an approach based on the use of regenerative abilities of own endogenous cells with high plasticity, in particular RPE cells and Muller glia. Currently, vertebrate RPE cells are of great interest as a source of new photoreceptors and other neurons in the degraded retina in vivo. In this regard, the possibilities of their direct reprogramming by genetic, epigenetic, chemical methods and their combination are investigated. The review focuses on research on gene reprogramming of vertebrate RPE cells into retinal neurons, with detailed analysis of the genes used as the main reprogramming factors, comparative analysis and extrapolation of experimental data from animals to humans. In addition, the review covers work on the use of alternative genetically-directed reprogramming approaches-chemically-mediated with the use of cocktails of therapeutic low-molecular compounds and microRNAs. In general, the results of research indicate the complexity of the process of reprogramming human RPE cells into retinal neurons. However, taking into account the results of reprogramming vertebrate cells, the availability of human RPE cells for various vectors that deliver a variety of molecules to cells: transcription factors, chimeric endonucleases, recombinant proteins and low-molecular compounds, we can assume the most optimal set of factors for the successful conversion of human RPE cells into retinal neurons.