{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:47:01Z","timestamp":1789181221568,"version":"build-2803163510"},"reference-count":57,"publisher":"National Academy of Sciences","issue":"11","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["EY033810"],"award-info":[{"award-number":["EY033810"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["EY030075"],"award-info":[{"award-number":["EY030075"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,3,12]]},"abstract":"<jats:p>\n                    Retinitis pigmentosa (RP) is a common form of retinal dystrophy that can be caused by mutations in any one of dozens of rod photoreceptor genes. The genetic heterogeneity of RP represents a significant challenge for the development of effective therapies. Here, we present evidence for a potential gene-independent therapeutic strategy based on targeting\n                    <jats:italic>Nr2e3<\/jats:italic>\n                    , a transcription factor required for the normal differentiation of rod photoreceptors.\n                    <jats:italic>Nr2e3<\/jats:italic>\n                    knockout results in hybrid rod photoreceptors that express the full complement of rod genes, but also a subset of cone genes. We show that germline deletion of\n                    <jats:italic>Nr2e3<\/jats:italic>\n                    potently protects rods in three mechanistically diverse mouse models of retinal degeneration caused by bright-light exposure (light damage), structural deficiency (rhodopsin-deficient\n                    <jats:italic>\n                      Rho\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice), or abnormal phototransduction (phosphodiesterase-deficient\n                    <jats:italic>rd10<\/jats:italic>\n                    mice).\n                    <jats:italic>Nr2e3<\/jats:italic>\n                    knockout confers strong neuroprotective effects on rods without adverse effects on their gene expression, structure, or function. Furthermore, in all three degeneration models, prolongation of rod survival by\n                    <jats:italic>Nr2e3<\/jats:italic>\n                    knockout leads to lasting preservation of cone morphology and function. These findings raise the possibility that upregulation of one or more cone genes in\n                    <jats:italic>Nr2e3<\/jats:italic>\n                    -deficient rods may be responsible for the neuroprotective effects we observe.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2316118121","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T13:46:23Z","timestamp":1709646383000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["Germline knockout of\n                    <i>Nr2e3<\/i>\n                    protects photoreceptors in three distinct mouse models of retinal degeneration"],"prefix":"10.1073","volume":"121","author":[{"given":"Alexander V.","family":"Kolesnikov","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4846-4608","authenticated-orcid":false,"given":"Daniel P.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph C.","family":"Corbo","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1659-008X","authenticated-orcid":false,"given":"Vladimir J.","family":"Kefalov","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/0470092645.ch3"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42258"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.33.1.89"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(2001)17:1<42::AID-HUMU5>3.0.CO;2-K"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2018.03.005"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69740-7"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2019-106473"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0012-9"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1214387110"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9072224"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14716"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000643"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.10.074"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/7678"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes9020068"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng774"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408183101"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.10.074"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0010011"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3571-04.2005"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.10.5551"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1245-14.2014"},{"key":"e_1_3_4_23_2","first-page":"252","article-title":"Gene expression in the mouse retina: The effect of damaging light","volume":"6","author":"Grimm C.","year":"2000","unstructured":"C. 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