Molecular Factors of the Maintenance and Activation of the Juvenile Phenotype of Cellular Sources for Eye Tissue Regeneration.

Modern achievements in the understanding of tissue regeneration, identification of endogenous cell sources for regeneration, and development of approaches for induction and differentiation of pluripotent stem cells have open broad prospects for regenerative medicine. However, application of the obtained information in medicine is hindered by insufficient knowledge on the molecular factors and their combinations capable of regulating the age and fate of cellular sources for eye tissue reparation as well as on the regenerative responses of these cells. In the review, we present our own and literature data on cells serving as endogenous sources for eye tissue regeneration in lower and higher vertebrates and properties of gene expression that allow these cells to maintain their juvenile phenotype. Transcription factors and signal pathways providing cell juvenile status as well as cell reprogramming and entry into the S-phase are discussed. The role of systemic factors (blood and immune system factors, hormones, oxidative stress products, and cell rejuvenation factors) in these processes and their interaction with local factors of the cell environment are described. Molecular factors and conditions for induction of reprogramming and proliferation of cellular sources involved in regeneration in vitro are analyzed with special attention to the role of epigenetic factors (associated with cell senescence, in particular) in the source cells conversion during eye tissue regeneration.