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Sector RP is a form of RP where degeneration originates in the inferior retina, mainly influenced by light exposure. Over 200\n                    <jats:italic>RHO<\/jats:italic>\n                    variants are pathogenic and associated with autosomal dominant RP.\n                    <jats:italic>RHO<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>M39R<\/jats:italic>\n                    <\/jats:sup>\n                    is one of the most common\n                    <jats:italic>RHO<\/jats:italic>\n                    variants linked to sector RP in the UK. A knock-in (KI) mouse model expressing\n                    <jats:italic>Rho<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>M39R<\/jats:italic>\n                    <\/jats:sup>\n                    was generated and characterised to investigate the mechanisms of degeneration associated with this variant and explore novel therapeutic strategies for rhodopsin sector RP. Under cyclic ambient light,\n                    <jats:italic>Rho<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>M39R\/+<\/jats:italic>\n                    <\/jats:sup>\n                    KI mice exhibited impaired retinal function by ERG, with some defects in OS ultrastructure, but retained normal outer nuclear layer (ONL) thickness. Repeated exposure to bright light led to photoreceptor loss. In contrast,\n                    <jats:italic>Rho<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>M39R\/M39R<\/jats:italic>\n                    <\/jats:sup>\n                    KI mice in cyclic ambient light displayed severe retinal dysfunction, ONL thinning, and grossly abnormal OS ultrastructure. In homozygous mice, a single bright light exposure significantly reduced ONL thickness within 48\u2009h. The rescue of these models was achieved through reduced light exposure and pharmacological intervention. Rearing in dim red light (red cage condition) restored ERG responses in\n                    <jats:italic>Rho<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>M39R\/+<\/jats:italic>\n                    <\/jats:sup>\n                    KI mice and improved ONL thickness in\n                    <jats:italic>Rho<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>M39R\/M39R<\/jats:italic>\n                    <\/jats:sup>\n                    KI mice. Transcriptomic analysis in\n                    <jats:italic>Rho<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>M39R\/M39R<\/jats:italic>\n                    <\/jats:sup>\n                    KI mice revealed upregulation of Sphingosine 1-P Receptor (\n                    <jats:italic>S1pr<\/jats:italic>\n                    ) transcripts. Treatment with the S1PR agonist Fingolimod (FTY720) before bright light exposure significantly reduced degeneration, demonstrating a protective effect in both heterozygous and homozygous models and suggesting potential as a therapeutic approach for sector RP patients.\n                  <\/jats:p>","DOI":"10.1038\/s41420-025-02769-2","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:10:20Z","timestamp":1761052220000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Preventing light-induced toxicity in a new mouse model of sector retinitis pigmentosa caused by Rhodopsin M39R variant"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5989-2962","authenticated-orcid":false,"given":"Rosellina","family":"Guarascio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5853-2099","authenticated-orcid":false,"given":"Kalliopi","family":"Ziaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwan-Leong","family":"Hau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Piccolo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara Eliza","family":"Nieuwenhuis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Bakoulina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rowan","family":"Asfahani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Aguil\u00e0","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitra","family":"Athanasiou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Sefic Svara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6429-654X","authenticated-orcid":false,"given":"Michael E.","family":"Cheetham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"2769_CR1","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","volume":"368","author":"DT Hartong","year":"2006","unstructured":"Hartong DT, Berson EL, Dryja TP. 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