Cell Sources for Retinal Regeneration: Implication for Data Translation in Biomedicine of the Eye

Abstract

The main degenerative diseases of the retina include macular degeneration, proliferative vitreoretinopathy, retinitis pigmentosa, and glaucoma. Novel approaches for treating retinal diseases are based on cell replacement therapy using a variety of exogenous stem cells. An alternative and complementary approach is the potential use of retinal regeneration cell sources (RRCSs) containing retinal pigment epithelium, ciliary body, Müller glia, and retinal ciliary region. RRCSs in lower vertebrates in vivo and in mammals mostly in vitro are able to proliferate and exhibit gene expression and epigenetic characteristics typical for neural/retinal cell progenitors. Here, we review research on the factors controlling the RRCSs’ properties, such as the cell microenvironment, growth factors, cytokines, hormones, etc., that determine the regenerative responses and alterations underlying the RRCS-associated pathologies. We also discuss how the current data on molecular features and regulatory mechanisms of RRCSs could be translated in retinal biomedicine with a special focus on (1) attempts to obtain retinal neurons de novo both in vivo and in vitro to replace damaged retinal cells; and (2) investigations of the key molecular networks stimulating regenerative responses and preventing RRCS-related pathologies.

Recent Achievements in the Heterogeneity of Mammalian and Human Retinal Pigment Epithelium: In Search of a Stem Cell

“…On the other hand, the different results may be explained by zonal differences, and, accordingly, by the contribution of the subpopulations of the RPE cells analyzed in in vitro systems. It cannot be excluded that oct4 can be expressed in pulses, as has been shown in the examples of Müller cell transdifferentiation in the retinas of mice and zebrafish [135,136]. However, OCT4 expression may meet a stoichiometric requirement that will allow cells to enter a multipotent state [137,138].…”

Impact of Microgravity and Other Spaceflight Factors on Retina of Vertebrates and Humans In Vivo and In Vitro

“…When studying the regeneration of eye tissues of newts exposed to r-μg and s-μg, we managed to obtain evidence of changes in the population of Müller glia (MG) cells of the retina [ 79 ]. MG, as a highly specialized cell population [ 80 ] showing certain resemblance with neural stem cells [ 81 ], is considered a potential resource for the vertebrate retina regeneration [ 82 , 83 , 84 , 85 ]. However, MG cells in mammals often respond to retinal damage by reactive gliosis.…”