{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:47:25Z","timestamp":1789991245845,"version":"4.0.1"},"reference-count":42,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","aaojournal.org","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Ophthalmology"],"published-print":{"date-parts":[[2016,10]]},"DOI":"10.1016\/j.ophtha.2016.06.041","type":"journal-article","created":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T03:31:18Z","timestamp":1474428678000},"page":"S98-S106","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":71,"special_numbering":"S","title":["Gene Therapy and Stem Cell Transplantation in Retinal Disease: The New Frontier"],"prefix":"10.1016","volume":"123","author":[{"given":"Robert E.","family":"MacLaren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-2106","authenticated-orcid":false,"given":"Steven D.","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ophtha.2016.06.041_bib1","doi-asserted-by":"crossref","first-page":"a017111","DOI":"10.1101\/cshperspect.a017111","article-title":"Clinical characteristics and current therapies for inherited retinal degenerations","volume":"5","author":"Sahel","year":"2014","journal-title":"Cold Spring Harb Perspect Med"},{"key":"10.1016\/j.ophtha.2016.06.041_bib2","doi-asserted-by":"crossref","first-page":"R9","DOI":"10.1093\/hmg\/ddu124","article-title":"Stem cells for investigation and treatment of inherited retinal disease","volume":"23","author":"Tucker","year":"2014","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.ophtha.2016.06.041_bib3","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/nbt.3513","article-title":"Targeted gene addition in human CD34(+) hematopoietic cells for correction of X-linked chronic granulomatous disease","volume":"34","author":"De Ravin","year":"2016","journal-title":"Nat Biotechnol"},{"key":"10.1016\/j.ophtha.2016.06.041_bib4","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1038\/gt.2010.56","article-title":"rAAV2\/5 gene-targeting to rods: dose-dependent efficiency and complications associated with different promoters","volume":"17","author":"Beltran","year":"2010","journal-title":"Gene Ther"},{"key":"10.1016\/j.ophtha.2016.06.041_bib5","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1089\/hum.2012.125","article-title":"The human rhodopsin kinase promoter in an AAV5 vector confers rod- and cone-specific expression in the primate retina","volume":"23","author":"Boye","year":"2012","journal-title":"Hum Gene Ther"},{"key":"10.1016\/j.ophtha.2016.06.041_bib6","doi-asserted-by":"crossref","first-page":"189ra76","DOI":"10.1126\/scitranslmed.3005708","article-title":"In\u00a0vivo-directed evolution of a new adeno-associated virus for therapeutic outer retinal gene delivery from the vitreous","volume":"5","author":"Dalkara","year":"2013","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.ophtha.2016.06.041_bib7","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0140-6736(14)61376-3","article-title":"Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1\/2 studies","volume":"385","author":"Schwartz","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.ophtha.2016.06.041_bib8","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1016\/S0140-6736(09)61836-5","article-title":"Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial","volume":"374","author":"Maguire","year":"2009","journal-title":"Lancet"},{"key":"10.1016\/j.ophtha.2016.06.041_bib9","doi-asserted-by":"crossref","first-page":"E517","DOI":"10.1073\/pnas.1218933110","article-title":"Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement","volume":"110","author":"Cideciyan","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ophtha.2016.06.041_bib10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1001\/archophthalmol.2011.298","article-title":"Gene therapy for Leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years","volume":"130","author":"Jacobson","year":"2012","journal-title":"Arch Ophthalmol"},{"key":"10.1016\/j.ophtha.2016.06.041_bib11","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1056\/NEJMoa1412965","article-title":"Improvement and decline in vision with gene therapy in childhood blindness","volume":"372","author":"Jacobson","year":"2015","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.ophtha.2016.06.041_bib12","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1089\/humc.2015.29004.sch","article-title":"Investor outlook: significance of the positive LCA2 gene therapy phase III results","volume":"26","author":"Schimmer","year":"2015","journal-title":"Hum Gene Ther Clin Devel"},{"key":"10.1016\/j.ophtha.2016.06.041_bib13","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/S0140-6736(13)62117-0","article-title":"Retinal gene therapy in patients with choroideremia: initial findings from a phase 1\/2 clinical trial","volume":"383","author":"MacLaren","year":"2014","journal-title":"Lancet"},{"key":"10.1016\/j.ophtha.2016.06.041_bib14","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1056\/NEJMc1509501","article-title":"Visual acuity after retinal gene therapy for choroideremia","volume":"374","author":"Edwards","year":"2016","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.ophtha.2016.06.041_bib15","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s00439-016-1637-y","article-title":"Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial","volume":"135","author":"Ghazi","year":"2016","journal-title":"Hum Genet"},{"key":"10.1016\/j.ophtha.2016.06.041_bib16","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/mt.2008.301","article-title":"Improved retinal function in a mouse model of dominant retinitis pigmentosa following AAV-delivered gene therapy","volume":"17","author":"Chadderton","year":"2009","journal-title":"Mol Ther"},{"key":"10.1016\/j.ophtha.2016.06.041_bib17","doi-asserted-by":"crossref","first-page":"e43251","DOI":"10.1371\/journal.pone.0043251","article-title":"Expression of wild-type Rp1 protein in Rp1 knock-in mice rescues the retinal degeneration phenotype","volume":"7","author":"Liu","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ophtha.2016.06.041_bib18","first-page":"384","article-title":"A\u00a0large deletion in the adRP gene PRPF31: evidence that haploinsufficiency is the cause of disease","volume":"12","author":"Abu-Safieh","year":"2006","journal-title":"Mol Vis"},{"key":"10.1016\/j.ophtha.2016.06.041_bib19","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1093\/hmg\/ddu005","article-title":"PRPF4 mutations cause autosomal dominant retinitis pigmentosa","volume":"23","author":"Chen","year":"2014","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.ophtha.2016.06.041_bib20","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.preteyeres.2014.08.001","article-title":"Vector platforms for gene therapy of inherited retinopathies","volume":"43","author":"Trapani","year":"2014","journal-title":"Prog Retin Eye Res"},{"key":"10.1016\/j.ophtha.2016.06.041_bib21","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/gt.2011.153","article-title":"Ocular gene delivery using lentiviral vectors","volume":"19","author":"Balaggan","year":"2012","journal-title":"Gene Ther"},{"key":"10.1016\/j.ophtha.2016.06.041_bib22","doi-asserted-by":"crossref","first-page":"4061","DOI":"10.1167\/iovs.13-11871","article-title":"Transduction of photoreceptors with equine infectious anemia virus lentiviral vectors: safety and biodistribution of StarGen for Stargardt disease","volume":"54","author":"Binley","year":"2013","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2016.06.041_bib23","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.jconrel.2015.10.007","article-title":"Non-viral therapeutic approaches to ocular diseases: an overview and future directions","volume":"219","author":"Zulliger","year":"2015","journal-title":"J\u00a0Control Release"},{"key":"10.1016\/j.ophtha.2016.06.041_bib24","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1126\/science.aad5177","article-title":"In\u00a0vivo gene editing in dystrophic mouse muscle and muscle stem cells","volume":"351","author":"Tabebordbar","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.ophtha.2016.06.041_bib25","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1016\/S0140-6736(15)00345-1","article-title":"Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial","volume":"386","author":"Rakoczy","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.ophtha.2016.06.041_bib26","doi-asserted-by":"crossref","first-page":"3896","DOI":"10.1073\/pnas.0600236103","article-title":"Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants","volume":"103","author":"Sieving","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ophtha.2016.06.041_bib27","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1038\/mt.2015.68","article-title":"CNTF gene therapy confers lifelong neuroprotection in a mouse model of human retinitis pigmentosa","volume":"23","author":"Lipinski","year":"2015","journal-title":"Mol Ther"},{"key":"10.1016\/j.ophtha.2016.06.041_bib28","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1006\/exer.2002.1176","article-title":"Effects of adeno-associated virus-vectored ciliary neurotrophic factor on retinal structure and function in mice with a P216L rds\/peripherin mutation","volume":"74","author":"Bok","year":"2002","journal-title":"Exp Eye Res"},{"key":"10.1016\/j.ophtha.2016.06.041_bib29","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1006\/mthe.2001.0473","article-title":"Long-term protection of retinal structure but not function using RAAV.CNTF in animal models of retinitis pigmentosa","volume":"4","author":"Liang","year":"2001","journal-title":"Mol Ther"},{"key":"10.1016\/j.ophtha.2016.06.041_bib30","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.cell.2015.03.023","article-title":"Rod-derived cone viability factor promotes cone survival by stimulating aerobic glycolysis","volume":"161","author":"Ait-Ali","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.ophtha.2016.06.041_bib31","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/gt.2011.155","article-title":"Optogenetic therapy for retinitis pigmentosa","volume":"19","author":"Busskamp","year":"2012","journal-title":"Gene Ther"},{"key":"10.1016\/j.ophtha.2016.06.041_bib32","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.1167\/iovs.04-0118","article-title":"Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: a prospective trial","volume":"45","author":"Binder","year":"2004","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2016.06.041_bib33","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.ophtha.2006.06.049","article-title":"Autologous transplantation of the retinal pigment epithelium and choroid in the treatment of neovascular age-related macular degeneration","volume":"114","author":"MacLaren","year":"2007","journal-title":"Ophthalmology"},{"key":"10.1016\/j.ophtha.2016.06.041_bib34","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ajo.2011.06.007","article-title":"A\u00a0free retinal pigment epithelium-choroid graft in patients with exudative age-related macular degeneration: results up to 7 years","volume":"153","author":"Van Zeeburg","year":"2012","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.ophtha.2016.06.041_bib35","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.ophtha.2016.06.041_bib36","doi-asserted-by":"crossref","first-page":"139","DOI":"10.2174\/1566523211313020008","article-title":"Translating induced pluripotent stem cells from bench to bedside: application to retinal diseases","volume":"13","author":"Cramer","year":"2013","journal-title":"Curr Gene Ther"},{"key":"10.1016\/j.ophtha.2016.06.041_bib37","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/513287a","article-title":"Japan stem-cell trial stirs envy","volume":"513","author":"Reardon","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.ophtha.2016.06.041_bib38","first-page":"3167","article-title":"Transplanted photoreceptors identified in dystrophic mouse retina by a transgenic reporter gene","volume":"32","author":"Gouras","year":"1991","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ophtha.2016.06.041_bib39","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1006\/exnr.1999.7157","article-title":"Photoreceptor layer reconstruction in a rodent model of retinal degeneration","volume":"159","author":"Kwan","year":"1999","journal-title":"Exp Neurol"},{"key":"10.1016\/j.ophtha.2016.06.041_bib40","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.ajo.2008.04.009","article-title":"Vision improvement in retinal degeneration patients by implantation of retina together with retinal pigment epithelium","volume":"146","author":"Radtke","year":"2008","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.ophtha.2016.06.041_bib41","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1073\/pnas.1119416110","article-title":"Reversal of end-stage retinal degeneration and restoration of visual function by photoreceptor transplantation","volume":"110","author":"Singh","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ophtha.2016.06.041_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/S0140-6736(16)30371-3","article-title":"Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial","author":"Bennett","year":"2016","journal-title":"Lancet"}],"container-title":["Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0161642016305097?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0161642016305097?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,9,8]],"date-time":"2018-09-08T03:57:55Z","timestamp":1536379075000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0161642016305097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["S0161642016305097"],"URL":"https:\/\/doi.org\/10.1016\/j.ophtha.2016.06.041","relation":{},"ISSN":["0161-6420"],"issn-type":[{"value":"0161-6420","type":"print"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Gene Therapy and Stem Cell Transplantation in Retinal Disease: The New Frontier","name":"articletitle","label":"Article Title"},{"value":"Ophthalmology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ophtha.2016.06.041","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 by the American Academy of Ophthalmology","name":"copyright","label":"Copyright"}]}}