{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T08:50:22Z","timestamp":1787475022020,"version":"build-2736575974"},"reference-count":71,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T00:00:00Z","timestamp":1467763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001708","name":"International Foundation for Research in Paraplegia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008240","name":"Fonds de Recherche du Qu\u00e9bec-Soci\u00e9t\u00e9 et Culture","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008240","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>In this study, we used a classical optic nerve injury model to address the function of the sphingosine 1\u2010phosphate (S1P)\u2013S1P receptor (S1PR) axis in retinal ganglion cell (RGC) death and axonal growth. After lesion, the expression of S1PR1 was generally reduced in axotomized RGCs but persisted in \u03b1RGCs, a subpopulation of injury\u2010resistant RGCs. Silencing S1PR1 with an adeno\u2010associated virus serotype 2 (AAV2) containing a shRNA specific to S1PR1 (AAV2.shRNA\u2010S1PR1) exacerbated the loss of RGCs induced by optic nerve crush; the rate of RGC survival was decreased by more than 24% in retinae infected with AAV2.shRNA\u2010S1PR1 compared with AAV2.shRNA\u2010scrambled or AAV2.GFP control treatments. In the superior and temporal regions of the retina, cell death rose by more than ~\u00a035% and ~\u00a050%, respectively, in comparison with control groups. In the optic nerve, S1PR1 silencing markedly reduced axonal sprouting after the lesion relative to control animals. Early after optic nerve crush, 67% of \u03b1RGCs stained for osteopontin were lost in retinae infected with AAV2.shRNA\u2010S1PR1, whereas the number of intrinsically photosensitive RGCs expressing melanopsin, another injury\u2010resistant RGC type, was not affected. Moreover, retinal infection with AAV2.shRNA\u2010S1PR1 down\u2010regulated mammalian target of rapamycin pathway activation in \u03b1RGCs. Together, our results reveal that S1PR1 contributes to survival and growth mechanisms in injured RGCs by regulating the mammalian target of rapamycin pathway.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13701-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>The role of sphingosine 1\u2010phosphate receptor 1 (S1PR1) was studied in retinal ganglion cell survival and axonal growth after optic nerve injury. After axonal damage, S1PR1 expression was decreased in retinal neurons. Viral\u2010mediated S1PR1 down\u2010regulation enhanced injury\u2010induced cell death and reduced spontaneous axonal growth. In injury\u2010resistant retinal neurons, the activation of mTOR signalling was down\u2010regulated by silencing S1PR1, suggesting an important role for S1PR1 in neuronal growth and survival mechanisms <jats:italic>in\u00a0vivo<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13701","type":"journal-article","created":{"date-parts":[[2016,6,16]],"date-time":"2016-06-16T15:53:38Z","timestamp":1466092418000},"page":"571-586","source":"Crossref","is-referenced-by-count":24,"title":["Sphingosine 1\u2010phosphate receptor 1 is required for retinal ganglion cell survival after optic nerve trauma"],"prefix":"10.1111","volume":"138","author":[{"given":"Sandrine","family":"Joly","sequence":"first","affiliation":[{"name":"CUO\u2010Recherche Centre de recherche du CHU de Qu\u00e9bec and D\u00e9partement d'ophtalmologie Facult\u00e9 de m\u00e9decine Universit\u00e9 Laval Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Pernet","sequence":"additional","affiliation":[{"name":"CUO\u2010Recherche Centre de recherche du CHU de Qu\u00e9bec and D\u00e9partement d'ophtalmologie Facult\u00e9 de m\u00e9decine Universit\u00e9 Laval Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,7,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-07-04368.1994"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3931-04.2005"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200176200"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/2051-5960-2-12"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-10-03977.2002"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-19-08367.1999"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.02.079"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-7431(02)00037-4"},{"key":"e_1_2_7_10_1","first-page":"2814","article-title":"Intrinsically photosensitive retinal ganglion cells are resistant to N\u2010methyl\u2010D\u2010aspartic acid excitotoxicity","volume":"18","author":"DeParis S.","year":"2012","journal-title":"Mol. 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