{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:52:26Z","timestamp":1790747546106,"version":"4.1.0"},"reference-count":65,"publisher":"Society for Neuroscience","issue":"44","license":[{"start":{"date-parts":[[2014,4,30]],"date-time":"2014-04-30T00:00:00Z","timestamp":1398816000000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2013,10,30]]},"abstract":"<jats:p>Interphotoreceptor retinoid-binding protein (IRBP) secreted by photoreceptors plays a pivotal role in photoreceptor survival with an unknown mechanism. A mutation in the human<jats:italic>IRBP<\/jats:italic>has been linked to retinitis pigmentosa, a progressive retinal degenerative disease. Mice lacking IRBP display severe early and progressive photoreceptor degeneration. However, the signaling pathway(s) leading to photoreceptor death in IRBP-deficient mice remains poorly understood. Here, we show that amounts of tumor necrosis factor-\u03b1 (TNF-\u03b1) in the interphotoreceptor matrix and retinas of<jats:italic>Irbp<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice were increased more than 10-fold and fivefold, respectively, compared with those in wild-type mice. Moreover, TNF-\u03b1 receptor 1, an important membrane death receptor that mediates both programmed apoptosis and necrosis, was also significantly increased in<jats:italic>Irbp<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>retina, and was colocalized with peanut agglutinin to the<jats:italic>Irbp<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>cone outer segments. Although these death signaling proteins were increased, the caspase-dependent and independent apoptotic pathways were mildly activated in the<jats:italic>Irbp<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>retinas, suggesting that other cell death mechanism(s) also contributes to the extensive photoreceptor degeneration in<jats:italic>Irbp<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>retina. We found that receptor interacting protein 1 and 3 (RIP1 and RIP3) kinases, the intracellular key mediators of TNF-induced cellular necrosis, were elevated at least threefold in the<jats:italic>Irbp<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>retinas. Moreover, pharmacological inhibition of RIP1 kinase significantly prevented cone and rod photoreceptor degeneration in<jats:italic>Irbp<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice. These results reveal that RIP kinase-mediated necrosis strongly contributes to cone and rod degeneration in<jats:italic>Irbp<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice, implicating the TNF-RIP pathway as a potential therapeutic target to prevent or delay photoreceptor degeneration in patients with retinitis pigmentosa caused by IRBP mutation.<\/jats:p>","DOI":"10.1523\/jneurosci.1380-13.2013","type":"journal-article","created":{"date-parts":[[2013,10,30]],"date-time":"2013-10-30T16:49:11Z","timestamp":1383151751000},"page":"17458-17468","source":"Crossref","is-referenced-by-count":85,"title":["Receptor Interacting Protein Kinase-Mediated Necrosis Contributes to Cone and Rod Photoreceptor Degeneration in the Retina Lacking Interphotoreceptor Retinoid-Binding Protein"],"prefix":"10.1523","volume":"33","author":[{"given":"Kota","family":"Sato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songhua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jibao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory I.","family":"Liou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel H.","family":"Travis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas G.","family":"Bazan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghao","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2013,10,30]]},"reference":[{"key":"2023041304074015000_33.44.17458.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1305"},{"key":"2023041304074015000_33.44.17458.2","doi-asserted-by":"crossref","first-page":"13677","DOI":"10.1016\/S0021-9258(17)38777-X","article-title":"Endogenous fatty acids are covalently and noncovalently bound to interphotoreceptor retinoid-binding protein in the monkey retina","volume":"260","author":"Bazan","year":"1985","journal-title":"J Biol Chem"},{"key":"2023041304074015000_33.44.17458.3","doi-asserted-by":"publisher","DOI":"10.1038\/385729a0"},{"key":"2023041304074015000_33.44.17458.4","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/S0021-9258(19)85061-5","article-title":"Interphotoreceptor retinoid-binding protein. 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