{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:42:57Z","timestamp":1789764177993,"version":"4.0.1"},"reference-count":44,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,5,2]],"date-time":"2019-05-02T00:00:00Z","timestamp":1556755200000},"content-version":"vor","delay-in-days":366,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2018,5]]},"DOI":"10.1016\/j.ymthe.2018.02.027","type":"journal-article","created":{"date-parts":[[2018,3,2]],"date-time":"2018-03-02T13:34:21Z","timestamp":1519997661000},"page":"1343-1353","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":45,"title":["Prevention of Photoreceptor Cell Loss in a Cln6 Mouse Model of Batten Disease Requires CLN6 Gene Transfer to Bipolar Cells"],"prefix":"10.1016","volume":"26","author":[{"given":"Sophia-Martha","family":"kleine Holthaus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Abelleira-Hervas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael A.","family":"Pearson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanai","family":"Duran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasios","family":"Georgiadis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Sampson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Rizzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Hoke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryea","family":"Maswood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selina","family":"Azam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich F.O.","family":"Luhmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara E.","family":"Mole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin R.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2018.02.027_bib1","series-title":"The Neuronal Ceroid Lipofuscinoses (Batten Disease)","author":"Mole","year":"2011"},{"key":"10.1016\/j.ymthe.2018.02.027_bib2","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1016\/j.bbadis.2013.01.019","article-title":"Cell biology and function of neuronal ceroid lipofuscinosis-related proteins","volume":"1832","author":"Kollmann","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ymthe.2018.02.027_bib3","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.ymthe.2006.01.006","article-title":"Gene therapy for lysosomal storage diseases","volume":"13","author":"Sands","year":"2006","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2018.02.027_bib4","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/0092-8674(95)90274-0","article-title":"Isolation of a novel gene underlying Batten disease, CLN3","volume":"82","author":"Consortium","year":"1995","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2018.02.027_bib5","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/j.bbadis.2013.04.008","article-title":"NCL diseases - clinical perspectives","volume":"1832","author":"Schulz","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ymthe.2018.02.027_bib6","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1089\/hum.2012.253","article-title":"Partial correction of the CNS lysosomal storage defect in a mouse model of juvenile neuronal ceroid lipofuscinosis by neonatal CNS administration of an adeno-associated virus serotype rh.10 vector expressing the human CLN3 gene","volume":"25","author":"Sondhi","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.ymthe.2018.02.027_bib7","doi-asserted-by":"crossref","first-page":"9669","DOI":"10.1523\/JNEUROSCI.1635-16.2016","article-title":"Self-Complementary AAV9 Gene Delivery Partially Corrects Pathology Associated with Juvenile Neuronal Ceroid Lipofuscinosis (CLN3)","volume":"36","author":"Bosch","year":"2016","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.ymthe.2018.02.027_bib8","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1093\/hmg\/ddq136","article-title":"Gene therapy rescues cone function in congenital achromatopsia","volume":"19","author":"Kom\u00e1romy","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ymthe.2018.02.027_bib9","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1093\/hmg\/ddr218","article-title":"Long-term and age-dependent restoration of visual function in a mouse model of CNGB3-associated achromatopsia following gene therapy","volume":"20","author":"Carvalho","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ymthe.2018.02.027_bib10","doi-asserted-by":"crossref","first-page":"6006","DOI":"10.1038\/ncomms7006","article-title":"Gene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179","volume":"6","author":"Nishiguchi","year":"2015","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2018.02.027_bib11","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.ophtha.2012.11.048","article-title":"Three-year follow-up after unilateral subretinal delivery of adeno-associated virus in patients with Leber congenital Amaurosis type 2","volume":"120","author":"Testa","year":"2013","journal-title":"Ophthalmology"},{"key":"10.1016\/j.ymthe.2018.02.027_bib12","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1056\/NEJMoa1414221","article-title":"Long-term effect of gene therapy on Leber\u2019s congenital amaurosis","volume":"372","author":"Bainbridge","year":"2015","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ymthe.2018.02.027_bib13","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1016\/j.ophtha.2016.03.003","article-title":"Results at 2\u00a0Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy","volume":"123","author":"Weleber","year":"2016","journal-title":"Ophthalmology"},{"key":"10.1016\/j.ymthe.2018.02.027_bib14","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.ymthe.2018.02.027_bib15","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.yexcr.2004.04.042","article-title":"CLN6, which is associated with a lysosomal storage disease, is an endoplasmic reticulum protein","volume":"298","author":"Mole","year":"2004","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.ymthe.2018.02.027_bib16","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/(SICI)1096-8628(19980526)77:4<289::AID-AJMG8>3.0.CO;2-I","article-title":"Neuronal ceroid lipofuscinosis (nclf), a new disorder of the mouse linked to chromosome 9","volume":"77","author":"Bronson","year":"1998","journal-title":"Am. J. Med. Genet."},{"key":"10.1016\/j.ymthe.2018.02.027_bib17","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1086\/338190","article-title":"Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse","volume":"70","author":"Gao","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ymthe.2018.02.027_bib18","doi-asserted-by":"crossref","first-page":"e75963","DOI":"10.1371\/journal.pone.0075963","article-title":"Progressive retinal degeneration and glial activation in the CLN6 (nclf) mouse model of neuronal ceroid lipofuscinosis: a beneficial effect of DHA and curcumin supplementation","volume":"8","author":"Mirza","year":"2013","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ymthe.2018.02.027_bib19","doi-asserted-by":"crossref","first-page":"6952","DOI":"10.1167\/iovs.13-12945","article-title":"Apoptotic photoreceptor loss and altered expression of lysosomal proteins in the nclf mouse model of neuronal ceroid lipofuscinosis","volume":"54","author":"Bartsch","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ymthe.2018.02.027_bib20","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nn.3032","article-title":"Transcriptional code and disease map for adult retinal cell types","volume":"15","author":"Siegert","year":"2012","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.ymthe.2018.02.027_bib21","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0896-6273(91)90122-G","article-title":"The retinal degeneration slow (rds) gene product is a photoreceptor disc membrane-associated glycoprotein","volume":"6","author":"Travis","year":"1991","journal-title":"Neuron"},{"key":"10.1016\/j.ymthe.2018.02.027_bib22","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1167\/iovs.05-0371","article-title":"Gene replacement therapy rescues photoreceptor degeneration in a murine model of Leber congenital amaurosis lacking RPGRIP","volume":"46","author":"Pawlyk","year":"2005","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ymthe.2018.02.027_bib23","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.crvi.2014.01.002","article-title":"Gene therapy for inherited retinal degenerations","volume":"337","author":"Dalkara","year":"2014","journal-title":"C.\u00a0R. Biol."},{"key":"10.1016\/j.ymthe.2018.02.027_bib24","doi-asserted-by":"crossref","first-page":"e62097","DOI":"10.1371\/journal.pone.0062097","article-title":"Targeting photoreceptors via intravitreal delivery using novel, capsid-mutated AAV vectors","volume":"8","author":"Kay","year":"2013","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ymthe.2018.02.027_bib25","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.15252\/emmm.201404077","article-title":"Efficient transduction and optogenetic stimulation of retinal bipolar cells by a synthetic adeno-associated virus capsid and promoter","volume":"6","author":"Cronin","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.ymthe.2018.02.027_bib26","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.ymthe.2018.02.027_bib27","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1006\/mcne.2002.1168","article-title":"Intravitreal injection of adeno-associated viral vectors results in the transduction of different types of retinal neurons in neonatal and adult rats: a comparison with lentiviral vectors","volume":"21","author":"Harvey","year":"2002","journal-title":"Mol. Cell. Neurosci."},{"key":"10.1016\/j.ymthe.2018.02.027_bib28","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1038\/mt.2009.181","article-title":"Inner limiting membrane barriers to AAV-mediated retinal transduction from the vitreous","volume":"17","author":"Dalkara","year":"2009","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2018.02.027_bib29","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1126\/science.2109351","article-title":"A promoter that drives transgene expression in cerebellar Purkinje and retinal bipolar neurons","volume":"248","author":"Oberdick","year":"1990","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2018.02.027_bib30","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3389\/fnins.2017.00161","article-title":"Present Molecular Limitations of ON-Bipolar Cell Targeted Gene Therapy","volume":"11","author":"van Wyk","year":"2017","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.ymthe.2018.02.027_bib31","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/0092-8674(95)90354-2","article-title":"Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene","volume":"80","author":"Masu","year":"1995","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2018.02.027_bib32","first-page":"2443","article-title":"A\u00a0naturally occurring mouse model of X-linked congenital stationary night blindness","volume":"39","author":"Pardue","year":"1998","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ymthe.2018.02.027_bib33","doi-asserted-by":"crossref","first-page":"6229","DOI":"10.1093\/hmg\/ddv341","article-title":"Intravitreal delivery of a novel AAV vector targets ON bipolar cells and restores visual function in a mouse model of complete congenital stationary night blindness","volume":"24","author":"Scalabrino","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ymthe.2018.02.027_bib34","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1085\/jgp.93.1.101","article-title":"B-wave of the electroretinogram. A\u00a0reflection of ON bipolar cell activity","volume":"93","author":"Stockton","year":"1989","journal-title":"J.\u00a0Gen. Physiol."},{"key":"10.1016\/j.ymthe.2018.02.027_bib35","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2147\/EB.S9078","article-title":"Energy metabolism of the visual system","volume":"2","author":"Wong-Riley","year":"2010","journal-title":"Eye Brain"},{"key":"10.1016\/j.ymthe.2018.02.027_bib36","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1089\/hum.2016.111","article-title":"Evaluation of dose and safety of AAV7m8 and AAV8BP2 in the non-human primate retina","volume":"28","author":"Ramachandran","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.ymthe.2018.02.027_bib37","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/gt.2013.64","article-title":"Tyrosine capsid-mutant AAV vectors for gene delivery to the canine retina from a subretinal or intravitreal approach","volume":"21","author":"Mowat","year":"2014","journal-title":"Gene Ther."},{"key":"10.1016\/j.ymthe.2018.02.027_bib38","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1136\/bjo.2006.091637","article-title":"Batten disease: features to facilitate early diagnosis","volume":"90","author":"Collins","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"10.1016\/j.ymthe.2018.02.027_bib39","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s00439-013-1381-5","article-title":"Next generation sequencing-based molecular diagnosis of retinitis pigmentosa: identification of a novel genotype-phenotype correlation and clinical refinements","volume":"133","author":"Wang","year":"2014","journal-title":"Hum. Genet."},{"key":"10.1016\/j.ymthe.2018.02.027_bib40","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.nbd.2010.09.011","article-title":"A knock-in reporter mouse model for Batten disease reveals predominant expression of Cln3 in visual, limbic and subcortical motor structures","volume":"41","author":"Ding","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.ymthe.2018.02.027_bib41","doi-asserted-by":"crossref","first-page":"e38310","DOI":"10.1371\/journal.pone.0038310","article-title":"Large-scale phenotyping of an accurate genetic mouse model of JNCL identifies novel early pathology outside the central nervous system","volume":"7","author":"Staropoli","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ymthe.2018.02.027_bib42","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/2051-5960-2-54","article-title":"Non-invasive assessment of retinal alterations in mouse models of infantile and juvenile neuronal ceroid lipofuscinosis by spectral domain optical coherence tomography","volume":"2","author":"Groh","year":"2014","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.ymthe.2018.02.027_bib43","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.jviromet.2004.07.001","article-title":"Purification of recombinant adeno-associated virus type 8 vectors by ion exchange chromatography generates clinical grade vector stock","volume":"121","author":"Davidoff","year":"2004","journal-title":"J.\u00a0Virol. Methods"},{"key":"10.1016\/j.ymthe.2018.02.027_bib44","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1016\/j.ophtha.2010.04.001","article-title":"Perifoveal m\u00fcller cell depletion in a case of macular telangiectasia type 2","volume":"117","author":"Powner","year":"2010","journal-title":"Ophthalmology"}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001618301035?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001618301035?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T22:22:37Z","timestamp":1556749357000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001618301035"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["S1525001618301035"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2018.02.027","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2018,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Prevention of Photoreceptor Cell Loss in a Cln6nclf Mouse Model of Batten Disease Requires CLN6 Gene Transfer to Bipolar Cells","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2018.02.027","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}]}}