CRISPR/Cas9-Mediated Models of Retinitis Pigmentosa Reveal Differential Proliferative Response of Müller Cells betweenand.

Abstract

Retinitis pigmentosa is an inherited retinal dystrophy that ultimately leads to blindness due to the progressive degeneration of rod photoreceptors and the subsequent non-cell autonomous death of cones.is the most frequently mutated gene in this disease. We here developedgene editing-based models of retinitis pigmentosa in twospecies,and, by using CRISPR/Cas9 technology. In both of them, loss offunction results in massive rod cell degeneration characterized by progressive shortening of outer segments and occasional cell death. This is followed by cone morphology deterioration. Despite these apparently similar degenerative environments, we found that Müller glial cells behave differently inand. While a significant proportion of Müller cells re-enter into the cell cycle in, their proliferation remains extremely limited in. This work thus reveals divergent responses to retinal injury in closely related species. These models should help in the future to deepen our understanding of the mechanisms that have shaped regeneration during evolution, with tremendous differences across vertebrates.