Comparative analysis of retinal remodeling (RR) after damage in species capable and incapable to mobilize endogenous cell reserves provides an insight as to how limitations on retina restoration in humans can be overcome. RR is a phenomenon accompanying the loss of photoreceptor cells in various diseases and experimental models. Our study on the adult newt and rat retinas damaged in vivo or cultured in vitro is an attempt to reveal universal and specific features of RR in the aspects of cell behavior and tissue anatomy. When newt retina is damaged by light in vivo or placed in tissue culture, a regenerative response is observed from four cell populations: retinal pigment epithelium (RPE), retinal growth zone, displaced bipolar-like cells, and macroglia. Cells of the first three populations migrate, divide, and differentiate to replace lost photoreceptors, while the macroglia shows a gliotic response. In the rat retina, RPE cells in damaged sites change their phenotype, migrate, rarely divide, and often undergo apoptosis; in parallel, interneurons move to the site of photoreceptor damage, and Muller cells respond by hypertrophy. Cells at the periphery of the rat retina are not involved in RR, and there are no signs of cell division and reprogramming for the functional replacement of lost neurons. Thus, RR events in the rat and newt are comparable, except that cell behavior during RR in the newt follows the developmental pattern and, hence, this process can be regarded as true retinal regeneration rather than mere retinal reconstruction, as in the rat.
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