Abstract
Stem cells have been part of the biomedical landscape since the early 1960s. However, the translation of stem cells to effective therapeutics have met significant challenges, especially for retinal diseases. The retina is a delicate and complex architecture of interconnected cells that are steadfastly interdependent. Degenerative mechanisms caused by acquired or inherited diseases disrupt this interconnectivity, devastating the retina and causing severe vision loss in many patients. Consequently, retinal differentiation of exogenous and endogenous stem cells is currently being explored as replacement therapies in the debilitating diseases. In this review, we will examine the mechanisms involved in exogenous stem cells differentiation and the challenges of effective integration to the host retina. Furthermore, we will explore the current advancements in trans-differentiation of endogenous stem cells, primarily Müller glia.
Highlights
INTRODUCTIONThe retina is a highly conserved tissue (Mitashov, 2004). unlike zebrafish and many amphibian species, the singular inability to regenerate damaged tissue in the mammalian retina has drastic ramifications
Amongst vertebrates, the retina is a highly conserved tissue (Mitashov, 2004)
Exploring the mechanism of exogenously and endogenously generated pluripotent stem cells is critical for the treatment of retinal degenerative diseases
Summary
The retina is a highly conserved tissue (Mitashov, 2004). unlike zebrafish and many amphibian species, the singular inability to regenerate damaged tissue in the mammalian retina has drastic ramifications. Embryonic, induced, and reprogrammed stem cells are pluripotent cells currently being explored for retinal cell replacement therapies. The adult eye is comprised of cells with dormant potency (Bernardos et al, 2007) These cells include Müller glia (Turner and Cepko, 1987; Bernardos et al, 2007) and cells derived from the ciliary pigment epithelia (Ballios et al, 2012; Jeon and Oh, 2015). Vision loss is an incredible challenge for treatment, especially in the post-mitotic environment of the retina Retinal diseases, such as retinitis pigmentosa (RP), tend to be heterogenic and highly varied, even in the event of mutations on the same locus (Wert et al, 2014; Verbakel et al, 2018). Exploring the mechanism of exogenously and endogenously generated pluripotent stem cells is critical for the treatment of retinal degenerative diseases. We will present the progress of elucidating the regenerative mechanisms involved in activating regenerative pathways in endogenous stem cells of the retina
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