{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:21:47Z","timestamp":1792167707729,"version":"4.4.0"},"reference-count":58,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Retinitis Pigmentosa (RP) is a group of rare, inherited, neurodegenerative diseases of the retina that primarily affect rod photoreceptors. The initial loss of rods is followed by a secondary cone photoreceptor degeneration and eventually legal blindness. Despite several attempts, RP still remains essentially untreatable. In recent years, inhibition of poly (ADP\u2010ribose) polymerase (PARP) has been proposed as a potential therapeutic strategy for autosomal\u2010recessive RP, based on promising work in preclinical animal models. However, the effects of PARP inhibitors in autosomal\u2010dominant RP are still largely unknown. Here, we employed a novel, human\u2010homologous rhodopsin\u2010mutant\n                    <jats:italic>Rho<\/jats:italic>\n                    <jats:sup>I255del\/+<\/jats:sup>\n                    mouse model for autosomal dominant RP to assess the impact of different PARP inhibitors on the progression of photoreceptor degeneration. The PARP inhibitors used \u2013olaparib, saruparib, INO1001, and nicotinamide\u2013target different PARP isoforms, and their potentially differential effects were evaluated in organotypic retinal explants cultivated under entirely defined conditions. Readouts comprised in\u00a0situ activity assays for PARP and calpain\u2010type proteases, the TUNEL assay for cell death, as well as immunostaining for activated calpain\u20102, activated caspase\u20103, rhodopsin, and cone arrestin\u20103. Unexpectedly, and in contrast to previous findings in animal models for recessive RP, all of the PARP inhibitors used led to marked and dose\u2010dependent rod photoreceptor toxicity in the\n                    <jats:italic>Rho<\/jats:italic>\n                    <jats:sup>I255del<\/jats:sup>\n                    dominant RP model. Furthermore, this effect appeared to be independent of rhodopsin expression. On the other hand, cone photoreceptors were apparently unaffected by PARP inhibition. The present study thus demonstrates the importance of PARP activity for rod photoreceptor viability in a dominant rhodopsin mutant, highlights the need for a deeper understanding of the mechanisms underlying photoreceptor degeneration in different RP forms, and cautions against the indiscriminate use of PARP inhibitors for the treatment of RP.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70319-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70319","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T13:13:57Z","timestamp":1766409237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>PARP<\/scp>\n                    Activity Is Essential for Retinal Photoreceptor Survival in the Human Homologous\n                    <i>Rho<\/i>\n                    <scp>\n                      <sup>I255del<\/sup>\n                    <\/scp>\n                    Mouse Model for Autosomal Dominant Retinitis Pigmentosa"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2727-1356","authenticated-orcid":false,"given":"Yu","family":"Zhu","sequence":"first","affiliation":[{"name":"Cell Death Mechanisms Group, Institute for Ophthalmic Research University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Graduate School for Cellular and Molecular Neuroscience 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