Cellular mechanisms of hereditary photoreceptor degeneration - Focus on cGMP.

Progress in Retinal and Eye Research
Michael PowerFrançois Paquet-Durand

Abstract

The cellular mechanisms underlying hereditary photoreceptor degeneration are still poorly understood, a problem that is exacerbated by the enormous genetic heterogeneity of this disease group. However, the last decade has yielded a wealth of new knowledge on degenerative pathways and their diversity. Notably, a central role of cGMP-signalling has surfaced for photoreceptor cell death triggered by a subset of disease-causing mutations. In this review, we examine key aspects relevant for photoreceptor degeneration of hereditary origin. The topics covered include energy metabolism, epigenetics, protein quality control, as well as cGMP- and Ca2+-signalling, and how the related molecular and metabolic processes may trigger photoreceptor demise. We compare and integrate evidence on different cell death mechanisms that have been associated with photoreceptor degeneration, including apoptosis, necrosis, necroptosis, and PARthanatos. A special focus is then put on the mechanisms of cGMP-dependent cell death and how exceedingly high photoreceptor cGMP levels may cause activation of Ca2+-dependent calpain-type proteases, histone deacetylases and poly-ADP-ribose polymerase. An evaluation of the available literature reveals that a large gro...Continue Reading

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Citations

Jul 9, 2020·Veterinary Ophthalmology·Paige A WinklerSimon M Petersen-Jones
Jul 29, 2020·Proceedings of the National Academy of Sciences of the United States of America·Norianne T IngramAlapakkam P Sampath
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