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Thome Memorial Foundation"},{"name":"Carl and Mildred Almen Reeves Foundation"},{"DOI":"10.13039\/100009784","name":"Starr Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009784","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bill and Emily Kuzma Family Gift for Retinal Research"},{"name":"Jeffrey Fort Innovation Fund"},{"DOI":"10.13039\/100001642","name":"Glenn Foundation for Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001642","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research to Prevent Blindness, Inc","award":["Unrestricted Grant to the Department of Ophthalmology"],"award-info":[{"award-number":["Unrestricted Grant to the Department of Ophthalmology"]}]},{"name":"Washington University in St. Louis Medical Scientist Training Program (NIH).","award":["T32 GM07200"],"award-info":[{"award-number":["T32 GM07200"]}]},{"name":"Research to Prevent Blindness Nelson Trust Award"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Leber congenital amaurosis type nine is an autosomal recessive retinopathy caused by mutations of the NAD\n                    <jats:sup>+<\/jats:sup>\n                    synthesis enzyme NMNAT1. Despite the ubiquitous expression of NMNAT1, patients do not manifest pathologies other than retinal degeneration. Here we demonstrate that widespread NMNAT1 depletion in adult mice mirrors the human pathology, with selective loss of photoreceptors highlighting the exquisite vulnerability of these cells to NMNAT1 loss. Conditional deletion demonstrates that NMNAT1 is required within the photoreceptor. Mechanistically, loss of NMNAT1 activates the NADase SARM1, the central executioner of axon degeneration, to trigger photoreceptor death and vision loss. Hence, the essential function of NMNAT1 in photoreceptors is to inhibit SARM1, highlighting an unexpected shared mechanism between axonal degeneration and photoreceptor neurodegeneration. These results define a novel SARM1-dependent photoreceptor cell death pathway and identifies SARM1 as a therapeutic candidate for retinopathies.\n                  <\/jats:p>","DOI":"10.7554\/elife.62027","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T06:00:21Z","timestamp":1603778421000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.62027","source":"Crossref","is-referenced-by-count":75,"title":["SARM1 depletion rescues NMNAT1-dependent photoreceptor cell death and retinal degeneration"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0024-0031","authenticated-orcid":true,"given":"Yo","family":"Sasaki","sequence":"first","affiliation":[{"name":"Department of Genetics, Washington University School of Medicine, St. Louis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kakita","sequence":"additional","affiliation":[{"name":"Department of Genetics, Washington University School of Medicine, St. Louis, United States"},{"name":"Department of Perinatal and Neonatal Medicine, Aichi Medical University, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Kubota","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdoulaye","family":"Sene","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2699-2573","authenticated-orcid":true,"given":"Tae Jun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norimitsu","family":"Ban","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6667-9018","authenticated-orcid":true,"given":"Joseph B","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8803-9369","authenticated-orcid":true,"given":"Sanford L","family":"Boye","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Powell Gene Therapy Center, Gainesville, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7262-0968","authenticated-orcid":true,"given":"Aaron","family":"DiAntonio","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Washington University School of Medicine, St. Louis, United States"},{"name":"Needleman Center for Neurometabolism and Axonal Therapeutics, St. Louis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7312-3197","authenticated-orcid":true,"given":"Shannon E","family":"Boye","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Cellular and Molecular Therapy, Gainesville, United 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