{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:06:33Z","timestamp":1785423993942,"version":"3.56.0"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01EY015289, R01EY018586, R01EY031492, R01EY026643"],"award-info":[{"award-number":["R01EY015289, R01EY018586, R01EY031492, R01EY026643"]}]},{"name":"NIH","award":["P30EY14801, P30EY002162"],"award-info":[{"award-number":["P30EY14801, P30EY002162"]}]},{"award":["R01EY015289, R01EY018586, R01EY031492, R01EY026643"],"award-info":[{"award-number":["R01EY015289, R01EY018586, R01EY031492, R01EY026643"]}],"id":[{"id":"https:\/\/ror.org\/044zkrt47","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30EY14801, P30EY002162"],"award-info":[{"award-number":["P30EY14801, P30EY002162"]}],"id":[{"id":"https:\/\/ror.org\/044zkrt47","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010849","name":"Hope for Vision","doi-asserted-by":"publisher","award":["Grant"],"award-info":[{"award-number":["Grant"]}],"id":[{"id":"10.13039\/100010849","id-type":"DOI","asserted-by":"publisher"}]},{"award":["Grant"],"award-info":[{"award-number":["Grant"]}],"id":[{"id":"https:\/\/ror.org\/02yqjk243","id-type":"ROR","asserted-by":"publisher"}]},{"name":"James and Esther King Biomedical Research Program of the State of Florida","award":["08KN-09, 2KF02"],"award-info":[{"award-number":["08KN-09, 2KF02"]}]},{"name":"Research to Prevent Blindness Inc.","award":["An unrestricted grant"],"award-info":[{"award-number":["An unrestricted grant"]}]},{"award":["An unrestricted grant"],"award-info":[{"award-number":["An unrestricted grant"]}],"id":[{"id":"https:\/\/ror.org\/04drjs621","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Private donation","award":["Retinal Degeneration Research"],"award-info":[{"award-number":["Retinal Degeneration Research"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Retinitis pigmentosa (RP) is a genetically heterogeneous group of inherited retinal degenerations with primary degeneration of rod photoreceptors followed by secondary cone loss. We investigated whether downregulating Nrl (neural retina leucine zipper), a key transcription factor specifying rod fate, can reprogram rods into a more resilient state. In a transgenic NrlN\/N mouse in which Nrl was markedly downregulated, the rod phenotype became more like a rod precursor, particularly in the inferior retina. Crossing NrlN\/N mice with two rod degeneration models, rd1 (Pde6brd1\/rd1) and rhodopsin P23H knock-in (RhoP23H\/P23H) mice, showed significantly improved photoreceptor survival in double-mutant mice. In addition, AAV-mediated delivery of shRNA targeting Nrl mRNA substantially enhanced photoreceptor survival in rd10 (Pde6brd10\/rd10) mice. These findings demonstrate that downregulation of Nrl reprograms rods and confers broad resistance to degeneration across multiple RP models. AAV-mediated Nrl knockdown represents a promising mutation-independent therapeutic strategy for autosomal recessive and dominant forms of RP.<\/jats:p>","DOI":"10.3390\/ijms27114683","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T16:06:08Z","timestamp":1779465968000},"page":"4683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Downregulating Nrl Expression and Rod Photoreceptor Protection"],"prefix":"10.3390","volume":"27","author":[{"given":"Yiwen","family":"Li","sequence":"first","affiliation":[{"name":"Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3690-3722","authenticated-orcid":false,"given":"Shuliang","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Florida International University, Miami, FL 33174, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weng","family":"Tao","sequence":"additional","affiliation":[{"name":"QOL Medical, LLC, Vero Beach, FL 32963, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wen","sequence":"additional","affiliation":[{"name":"Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.preteyeres.2018.03.005","article-title":"Non-syndromic retinitis pigmentosa","volume":"66","author":"Verbakel","year":"2018","journal-title":"Prog. 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