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While the correlation between poly-ADP-ribose polymerase (PARP) activity and the degeneration of rod photoreceptors is established in the <jats:italic>rd2<\/jats:italic> model, the specific mechanism driving cone degeneration in this model remains unclear. Furthermore, it is yet to be determined whether inhibiting PARP activity can effectively impede the degeneration of cone photoreceptors in this\u00a0context.\u00a0We demonstrated that PARP inhibitors Olaparib, BMN-673, and 3-aminobenzamide (3AB), effectively reduced photoreceptor cell loss in the <jats:italic>rd2<\/jats:italic> retina. Notably, <jats:italic>rd2<\/jats:italic> retinas exhibited decreased cone density, but treatment with PARP inhibitors significantly protected cone photoreceptors. The PARP inhibitors, particularly BMN-673, demonstrated a significant protective effect as evidenced by increased rhodopsin expression within the outer segment and a concurrent decrease in M\u00fcller cell activity indicated by GFAP expression. The treatment also resulted in significant changes for markers of oxidative stress, such as glutathione (GSH), and oxidized glutathione (GSSG). Notably, the administration of PARP inhibitors also reduced CD9 expression (extracellular vesicle marker), which were significantly increased within the outer nuclear layer (ONL) in the <jats:italic>rd2<\/jats:italic> retinas. Among PARP inhibitors, BMN-673 demonstrated the highest efficacy in preserving photoreceptors, particularly benefiting cone cells.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1186\/s40478-025-01982-5","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T12:01:35Z","timestamp":1743595295000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PARP inhibition preserves cone photoreceptors in rd2 retina"],"prefix":"10.1186","volume":"13","author":[{"given":"Pakize Nur","family":"Akkaya","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Miranda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inmaculada","family":"Almansa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cigdem","family":"Elmas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dragana","family":"Trifunovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zohreh","family":"Hosseinzadeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayse","family":"Sahaboglu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"issue":"1","key":"1982_CR1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41525-023-00388-3","volume":"9","author":"HJ Kao","year":"2024","unstructured":"Kao HJ, Lin TY, Hsieh FJ, Chien JY, Yeh EC, Lin WJ et al (2024) Highly efficient capture approach for the identification of diverse inherited retinal disorders. 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