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These cyclic processes are regulated by retinal circadian clocks, molecular machineries regulating gene expression across the 24\u2010h\u2009cycle. Although hundreds of genes associated with genetic retinal disorders have been identified, no direct link has been established with the clock. Hence, we investigated the hypothesis that a poorly functioning circadian clock aggravates retinal photoreceptor disease. We performed this study in the P23H rhodopsin\u2010mutated mouse model (P23H Rho) that mimics one major cause of human autosomal dominant retinitis pigmentosa. We also used the rod\u2010specific knockout (rod\u2010\n                    <jats:italic>Bmal1KO<\/jats:italic>\n                    ) of\n                    <jats:italic>Bmal1<\/jats:italic>\n                    , a key clock component. More specifically, we used either heterozygous P23H Rho mice or rod\u2010\n                    <jats:italic>Bmal1KO<\/jats:italic>\n                    alone, as well as double mutants of these strains and control mice. We showed by structural (histology, immunohistochemistry) and functional (electroretinography: ERG) analyses that the retinitis pigmentosa phenotype is exacerbated in the double mutant line compared to the P23H Rho mutation alone. Indeed, we observed marked ERG amplitude reduction and more photoreceptor cell loss in double mutants with respect to simple P23H Rho mutants. These observations were further corroborated by transcriptome analysis revealing major gene expression differences between these genotypes. In this data, we identified unique gene expression sets implicating neurogenesis, phototransduction cascade, and metabolism, associated with enhanced photoreceptor degeneration. Thus, our results establish a link between clock dysfunction and retinal degeneration and suggest underlying molecular mechanisms, together providing new concepts for understanding and managing blinding diseases.\n                  <\/jats:p>","DOI":"10.1096\/fj.202401967r","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T03:52:08Z","timestamp":1743738728000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Circadian clock disruption promotes retinal photoreceptor degeneration"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5182-2878","authenticated-orcid":false,"given":"Shumet T.","family":"Gegnaw","sequence":"first","affiliation":[{"name":"Centre National de la Recherche Scientifique Universit\u00e9 de Strasbourg, Institut Des Neurosciences Cellulaires et Int\u00e9gratives  Strasbourg France"},{"name":"Department of Human Genetics Amsterdam 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