{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:27:56Z","timestamp":1791221276508,"version":"4.1.0"},"reference-count":38,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2006,3,1]],"date-time":"2006-03-01T00:00:00Z","timestamp":1141171200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T00:00:00Z","timestamp":1475798400000},"content-version":"vor","delay-in-days":3873,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2006,3]]},"DOI":"10.1016\/j.ymthe.2005.09.001","type":"journal-article","created":{"date-parts":[[2005,10,12]],"date-time":"2005-10-12T11:09:17Z","timestamp":1129115357000},"page":"565-572","source":"Crossref","is-referenced-by-count":147,"title":["Gene Therapy Restores Vision-Dependent Behavior as Well as Retinal Structure and Function in a Mouse Model of RPE65 Leber Congenital Amaurosis"],"prefix":"10.1016","volume":"13","author":[{"given":"Ji-jing","family":"Pang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Nusinowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed M.","family":"Noorwez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asha","family":"Rani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Foster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vince A.","family":"Chiodo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Doyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huashi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritu","family":"Malhotra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline T.","family":"Teusner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Hugh","family":"McDowell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok-Hong","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalesh","family":"Kaushal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Hauswirth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2005.09.001_bib1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S0968-0004(01)01799-6","article-title":"Activation of rhodopsin: new insights from structural and biochemical studies","volume":"26","author":"Okada","year":"2001","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.ymthe.2005.09.001_bib2","doi-asserted-by":"crossref","first-page":"12592","DOI":"10.1021\/bi00165a008","article-title":"Mechanism of activation and inactivation of opsin: role of Glu113 and Lys296","volume":"31","author":"Cohen","year":"1992","journal-title":"Biochemistry"},{"key":"10.1016\/j.ymthe.2005.09.001_bib3","doi-asserted-by":"crossref","first-page":"13741","DOI":"10.1021\/bi00250a027","article-title":"Rod outer segment retinol dehydrogenase: substrate specificity and role in phototransduction","volume":"33","author":"Palczewski","year":"1994","journal-title":"Biochemistry"},{"key":"10.1016\/j.ymthe.2005.09.001_bib4","doi-asserted-by":"crossref","first-page":"20621","DOI":"10.1074\/jbc.271.34.20621","article-title":"Mechanisms of opsin activation","volume":"271","author":"Buczylko","year":"1996","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymthe.2005.09.001_bib5","doi-asserted-by":"crossref","first-page":"15701","DOI":"10.1016\/S0021-9258(19)49592-6","article-title":"The role of arrestin and retinoids in the regeneration pathway of rhodopsin","volume":"267","author":"Hofmann","year":"1992","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymthe.2005.09.001_bib6","doi-asserted-by":"crossref","first-page":"11034","DOI":"10.1074\/jbc.275.15.11034","article-title":"Identification and characterization of all-trans-retinol dehydrogenase from photoreceptor outer segments, the visual cycle enzyme that reduces all-trans-retinal to all-trans-retinol","volume":"275","author":"Rattner","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymthe.2005.09.001_bib7","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/S0042-6989(97)00198-3","article-title":"Reduction of all-trans-retinal limits regeneration of visual pigment in mice","volume":"38","author":"Saari","year":"1998","journal-title":"Vision Res."},{"key":"10.1016\/j.ymthe.2005.09.001_bib8","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1074\/jbc.270.3.1107","article-title":"The retinal pigment epithelial-specific 11-cis retinol dehydrogenase belongs to the family of short chain alcohol dehydrogenases","volume":"270","author":"Simon","year":"1995","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymthe.2005.09.001_bib9","doi-asserted-by":"crossref","first-page":"15751","DOI":"10.1016\/S0021-9258(18)82319-5","article-title":"Molecular cloning and expression of RPE65, a novel retinal pigment epithelium-specific microsomal protein that is post-transcriptionally regulated in vitro","volume":"268","author":"Hamel","year":"1993","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymthe.2005.09.001_bib10","doi-asserted-by":"crossref","first-page":"23035","DOI":"10.1016\/S0021-9258(18)50052-1","article-title":"Characterization of a plasma retinol-binding protein membrane receptor expressed in the retinal pigment epithelium","volume":"267","author":"Bavik","year":"1992","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymthe.2005.09.001_bib11","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.cell.2005.06.042","article-title":"Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium","volume":"122","author":"Jin","year":"2005","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2005.09.001_bib12","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/ng1097-194","article-title":"Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy","volume":"17","author":"Gu","year":"1997","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ymthe.2005.09.001_bib13","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1073\/pnas.95.6.3088","article-title":"Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis","volume":"95","author":"Morimura","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2005.09.001_bib14","first-page":"4293","article-title":"Genetics and phenotypes of RPE65 mutations in inherited retinal degeneration","volume":"41","author":"Thompson","year":"2000","journal-title":"Invest. Ophthalmol. Visual Sci."},{"key":"10.1016\/j.ymthe.2005.09.001_bib15","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1076\/1381-6810(200009)2131-ZFT135","article-title":"Mutational analysis and clinical correlation in Leber congenital amaurosis","volume":"21","author":"Dharmaraj","year":"2000","journal-title":"Ophthalmic Genet."},{"key":"10.1016\/j.ymthe.2005.09.001_bib16","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/ng0501-92","article-title":"Gene therapy restores vision in a canine model of childhood blindness","volume":"28","author":"Acland","year":"2001","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ymthe.2005.09.001_bib17","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1167\/iovs.02-0595","article-title":"Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog","volume":"44","author":"Narfstrom","year":"2003","journal-title":"Invest. Ophthalmol. Visual Sci."},{"key":"10.1016\/j.ymthe.2005.09.001_bib18","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/3813","article-title":"Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle","volume":"20","author":"Redmond","year":"1998","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ymthe.2005.09.001_bib19","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.ymthe.2003.11.013","article-title":"In utero gene therapy rescues vision in a murine model of congenital blindness","volume":"9","author":"Dejneka","year":"2004","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2005.09.001_bib20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1479-0556-2-3","article-title":"Recombinant adeno-associated virus type 2-mediated gene delivery into the Rpe65\u2212\/\u2212 knockout mouse eye results in limited rescue","volume":"2","author":"Lai","year":"2004","journal-title":"Genet. Vaccines Ther."},{"key":"10.1016\/j.ymthe.2005.09.001_bib21","doi-asserted-by":"crossref","first-page":"19173","DOI":"10.1074\/jbc.M112384200","article-title":"Recovery of visual functions in a mouse model of Leber congenital amaurosis","volume":"277","author":"Van Hooser","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymthe.2005.09.001_bib22","first-page":"152","article-title":"Retinal degeneration 12 (rd12): a new, spontaneously arising mouse model for human Leber congenital amaurosis (LCA)","volume":"11","author":"Pang","year":"2005","journal-title":"Mol. Vision"},{"key":"10.1016\/j.ymthe.2005.09.001_bib23","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0002-9394(03)00913-9","article-title":"Thirty-year follow-up of a patient with Leber congenital amaurosis and novel RPE65 mutations","volume":"137","author":"Al Khayer","year":"2004","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.ymthe.2005.09.001_bib24","first-page":"2735","article-title":"Early-onset severe rod-cone dystrophy in young children with RPE65 mutations","volume":"41","author":"Lorenz","year":"2000","journal-title":"Invest. Ophthalmol. Visual Sci."},{"key":"10.1016\/j.ymthe.2005.09.001_bib25","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1002\/jgm.278","article-title":"Prenatal human ocular degeneration occurs in Leber's congenital amaurosis (LCA2)","volume":"4","author":"Porto","year":"2002","journal-title":"J. Gene Med."},{"key":"10.1016\/j.ymthe.2005.09.001_bib26","doi-asserted-by":"crossref","first-page":"7651","DOI":"10.1128\/JVI.76.15.7651-7660.2002","article-title":"Virus-mediated transduction of murine retina with adeno-associated virus: effects of viral capsid and genome size","volume":"76","author":"Yang","year":"2002","journal-title":"J. Virol."},{"key":"10.1016\/j.ymthe.2005.09.001_bib27","first-page":"131","article-title":"Subretinal injections in rodent eyes: effects on electrophysiology and histology of rat retina","volume":"7","author":"Timmers","year":"2001","journal-title":"Mol. Vision"},{"key":"10.1016\/j.ymthe.2005.09.001_bib28","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/ng712","article-title":"New views on RPE65 deficiency: the rod system is the source of vision in a mouse model of Leber congenital amaurosis","volume":"29","author":"Seeliger","year":"2001","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ymthe.2005.09.001_bib29","doi-asserted-by":"crossref","first-page":"13662","DOI":"10.1073\/pnas.2234461100","article-title":"Isorhodopsin rather than rhodopsin mediates rod function in RPE65 knock-out mice","volume":"23","author":"Fan","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2005.09.001_bib30","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1086\/302335","article-title":"Different functional outcome of RetGC1 and RPE65 gene mutations in Leber congenital amaurosis","volume":"64","author":"Perrault","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ymthe.2005.09.001_bib31","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/ng1246","article-title":"Spontaneous activity of opsin apoprotein is a cause of Leber congenital amaurosis","volume":"35","author":"Woodruff","year":"2003","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ymthe.2005.09.001_bib32","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1006\/hbeh.1998.1475","article-title":"Sex differences in the activational effect of ERalpha on spatial learning","volume":"34","author":"Fugger","year":"1998","journal-title":"Horm. Behav."},{"key":"10.1016\/j.ymthe.2005.09.001_bib33","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1006\/exnr.1997.6642","article-title":"Correlates of photoreceptor rescue by transplantation of human fetal RPE in the RCS rat","volume":"149","author":"Little","year":"1998","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.ymthe.2005.09.001_bib34","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0166-4328(94)00168-F","article-title":"Analysis of severe photoreceptor loss and Morris water-maze performance in aged rats","volume":"68","author":"O'steen","year":"1995","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.ymthe.2005.09.001_bib35","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0166-4328(94)00167-E","article-title":"Water maze performance of aged Sprague\u2013Dawley rats in relation to retinal morphologic measures","volume":"68","author":"Spencer","year":"1995","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.ymthe.2005.09.001_bib36","first-page":"1604","article-title":"Identification of the RPE65 protein in mammalian cone photoreceptors","volume":"43","author":"Znoiko","year":"2002","journal-title":"Invest. Ophthalmol. Visual Sci."},{"key":"10.1016\/j.ymthe.2005.09.001_bib37","doi-asserted-by":"crossref","first-page":"6916","DOI":"10.1073\/pnas.94.13.6916","article-title":"Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus","volume":"94","author":"Flannery","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2005.09.001_bib38","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S0076-6879(00)16760-6","article-title":"Production and purification of recombinant adeno-associated virus","volume":"316","author":"Hauswirth","year":"2000","journal-title":"Methods Enzymol."}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001605015881?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001605015881?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,7,18]],"date-time":"2021-07-18T14:24:23Z","timestamp":1626618263000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001605015881"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,3]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2006,3]]}},"alternative-id":["S1525001605015881"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2005.09.001","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2006,3]]}}}