{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T17:10:27Z","timestamp":1768669827063,"version":"3.49.0"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY030081"],"award-info":[{"award-number":["EY030081"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY031674"],"award-info":[{"award-number":["EY031674"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Eye Research"],"published-print":{"date-parts":[[2023,1]]},"DOI":"10.1016\/j.exer.2022.109344","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T11:16:53Z","timestamp":1670584613000},"page":"109344","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Intravitreal gene therapy preserves retinal function in a canine model of CLN2 neuronal ceroid lipofuscinosis"],"prefix":"10.1016","volume":"226","author":[{"given":"Grace Robinson","family":"Kick","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca E.H.","family":"Whiting","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juri","family":"Ota-Kuroki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leilani J.","family":"Castaner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandie","family":"Morgan-Jack","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julianna C.","family":"Sabol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth J.","family":"Meiman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francheska","family":"Ortiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2582-9187","authenticated-orcid":false,"given":"Martin L.","family":"Katz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.exer.2022.109344_bib1","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.ymgme.2006.02.016","article-title":"A frame shift mutation in canine TPP1 (the ortholog of human CLN2) in a juvenile Dachshund with neuronal ceroid lipofuscinosis","volume":"89","author":"Awano","year":"2006","journal-title":"Mol. Genet. Metabol."},{"key":"10.1016\/j.exer.2022.109344_bib2","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1056\/NEJMoa1414221","article-title":"Long-term effect of gene therapy on leber's congenital amaurosis","volume":"372","author":"Bainbridge","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.exer.2022.109344_bib3","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.bbamcr.2008.10.016","article-title":"Sorting of lysosomal proteins","volume":"1793","author":"Braulke","year":"2009","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"10.1016\/j.exer.2022.109344_bib4","series-title":"The Neuronal Ceroid Lipofuscinoses (Batten Disease)","first-page":"80","article-title":"CLN2","author":"Chang","year":"2011"},{"key":"10.1016\/j.exer.2022.109344_bib5","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.clim.2018.09.003","article-title":"Immunogenicity to cerliponase alfa intracerebroventricular enzyme replacement therapy for CLN2 disease: results from a Phase 1\/2 study","volume":"197","author":"Cherukuri","year":"2018","journal-title":"Clin. Immunol."},{"key":"10.1016\/j.exer.2022.109344_bib6","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.ymgme.2011.12.012","article-title":"Mannose-6-phosphate pathway: a review on its role in lysosomal function and dysfunction","volume":"105","author":"Coutinho","year":"2012","journal-title":"Mol. Genet. Metabol."},{"key":"10.1016\/j.exer.2022.109344_bib7","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.exer.2022.109344_bib8","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1007\/s00417-021-05508-2","article-title":"Real-world outcomes of voretigene neparvovec treatment in pediatric patients with RPE65-associated Leber congenital amaurosis","volume":"260","author":"Deng","year":"2022","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"10.1016\/j.exer.2022.109344_bib9","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ajo.2018.06.011","article-title":"Two-Year results after AAV2-mediated gene therapy for choroideremia: the alberta experience","volume":"193","author":"Dimopoulos","year":"2018","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.exer.2022.109344_bib10","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1016\/j.jaapos.2019.08.018","article-title":"How long does gene therapy last? 4-year follow-up of phase 3 voretigene neparvovec trial in <em>RPE65<\/em>-associated LCA\/inherited retinal disease","volume":"23","author":"Drack","year":"2019","journal-title":"J. Am. Assoc. Pediatr. Ophthalmol. Strabis."},{"key":"10.1016\/j.exer.2022.109344_bib11","article-title":"Ongoing retinal degeneration despite intraventricular enzyme replacement therapy with cerliponase alfa in late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2 disease)","author":"Dulz","year":"2022","journal-title":"Br. J. Ophthalmol."},{"key":"10.1016\/j.exer.2022.109344_bib12","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s10633-013-9388-8","article-title":"Guidelines for clinical electroretinography in the dog: 2012 update","volume":"127","author":"Ekesten","year":"2013","journal-title":"Doc. Ophthalmol."},{"key":"10.1016\/j.exer.2022.109344_bib13","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.celrep.2019.06.013","article-title":"Neuronal soma-derived degradative lysosomes are continuously delivered to distal axons to maintain local degradation capacity","volume":"28","author":"Farfel-Becker","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.exer.2022.109344_bib14","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nrm1050","article-title":"Mannose 6-phosphate receptors: new twists in the tale","volume":"4","author":"Ghosh","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.exer.2022.109344_bib15","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.ymthe.2005.04.018","article-title":"AAV2-mediated ocular gene therapy for infantile neuronal ceroid lipofuscinosis","volume":"12","author":"Griffey","year":"2005","journal-title":"Mol. Ther."},{"key":"10.1016\/j.exer.2022.109344_bib16","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S0140-6736(17)30979-0","article-title":"Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial","volume":"390","author":"Heier","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.exer.2022.109344_bib17","first-page":"109\u201416","article-title":"Incomplete proteolysis may contribute to lipofuscin accumulation in the retinal pigment epithelium","volume":"266","author":"Katz","year":"1989","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.exer.2022.109344_bib18","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1167\/iovs.08-1712","article-title":"Retinal pathology in a canine model of late infantile neuronal ceroid lipofuscinosis","volume":"49","author":"Katz","year":"2008","journal-title":"Invest. Opthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2022.109344_bib19","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/jnr.23423","article-title":"Enzyme replacement therapy attenuates disease progression in a canine model of late\u2010infantile neuronal ceroid lipofuscinosis (CLN2 Disease)","volume":"92","author":"Katz","year":"2014","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.exer.2022.109344_bib20","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0047-6374(89)90065-1","article-title":"Development of lipofuscin-like fluorescence in the retinal pigment epithelium in response to protease inhibitor treatment","volume":"49","author":"Katz","year":"1989","journal-title":"Mech. Ageing Dev."},{"key":"10.1016\/j.exer.2022.109344_bib21","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aac6191","article-title":"AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease","volume":"7","author":"Katz","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.exer.2022.109344_bib22","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0014-4835(05)80213-1","article-title":"Influence of dietary vitamin a on autofluorescence of leupeptin-induced inclusions in the retinal pigment epithelium","volume":"54","author":"Katz","year":"1992","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109344_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.ophtha.2022.06.018","article-title":"Inflammation after voretigene neparvovec administration in patients with RPE65-related retinal dystrophy","author":"Kessel","year":"2022","journal-title":"Ophthalmology"},{"key":"10.1016\/j.exer.2022.109344_bib24","first-page":"1","article-title":"Gene therapy targeting the inner retina rescues the retinal phenotype in a mouse model of CLN3 Batten disease","author":"Kleine Holthaus","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.exer.2022.109344_bib25","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1016\/j.ymthe.2018.02.027","article-title":"Prevention of photoreceptor cell loss in a Cln6 nclf mouse model of batten disease requires CLN6 gene transfer to bipolar cells","volume":"26","author":"Kleine Holthaus","year":"2018","journal-title":"Mol. Ther."},{"key":"10.1016\/j.exer.2022.109344_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2022.105628","article-title":"Intravitreal gene therapy restores the autophagy-lysosomal pathway and attenuates retinal degeneration in cathepsin D-deficient mice","volume":"164","author":"Liu","year":"2022","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.exer.2022.109344_bib27","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.ophtha.2019.06.017","article-title":"Efficacy, safety, and durability of voretigene neparvovec-rzyl in RPE65 mutation\u2013associated inherited retinal dystrophy","volume":"126","author":"Maguire","year":"2019","journal-title":"Ophthalmology"},{"key":"10.1016\/j.exer.2022.109344_bib28","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1016\/j.bbadis.2015.05.011","article-title":"Genetics of the neuronal ceroid lipofuscinoses (Batten disease)","volume":"1852","author":"Mole","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.exer.2022.109344_bib29","series-title":"The Neuronal Ceroid Lipofuscinoses (Batten Disease)","year":"2011"},{"key":"10.1016\/j.exer.2022.109344_bib30","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.exer.2022.109344_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2021.108600","article-title":"Intravitreal gene therapy protects against retinal dysfunction and degeneration in sheep with CLN5 Batten disease","author":"Murray","year":"2021","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109344_bib32","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":"Narfstr\u00f6m","year":"2003","journal-title":"Invest. Opthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2022.109344_bib33","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2018-99-118334","article-title":"Adeno-associated mediated gene transfer for hemophilia B:8 Year follow up and impact of removing \u201cempty viral particles\u201d on safety and efficacy of gene transfer","volume":"132","author":"Nathwani","year":"2018","journal-title":"Blood"},{"key":"10.1016\/j.exer.2022.109344_bib34","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.yrtph.2009.03.012","article-title":"Immunogenicity of biologically-derived therapeutics: assessment and interpretation of nonclinical safety studies","volume":"54","author":"Ponce","year":"2009","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.exer.2022.109344_bib35","first-page":"1","article-title":"Neuronal endolysosomal transport and lysosomal functionality in maintaining axonostasis","volume":"221","author":"Roney","year":"2022","journal-title":"JCB (J. Cell Biol.)"},{"key":"10.1016\/j.exer.2022.109344_bib36","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0140-6736(17)31868-8","article-title":"Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial","volume":"390","author":"Russell","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.exer.2022.109344_bib37","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1056\/NEJMoa1712649","article-title":"Study of intraventricular cerliponase alfa for CLN2 disease","volume":"378","author":"Schulz","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.exer.2022.109344_bib38","doi-asserted-by":"crossref","DOI":"10.1126\/science.277.5333.1802","article-title":"Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis","volume":"277","author":"Sleat","year":"1997","journal-title":"Science"},{"key":"10.1016\/j.exer.2022.109344_bib39","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2147\/TCRM.S241048","article-title":"Changing times for CLN2 disease: the era of enzyme replacement therapy","volume":"16","author":"Specchio","year":"2020","journal-title":"Therapeut. Clin. Risk Manag."},{"key":"10.1016\/j.exer.2022.109344_bib40","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/ajmg.10660","article-title":"Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations","volume":"112","author":"Steinfeld","year":"2002","journal-title":"Am. J. Med. Genet."},{"key":"10.1016\/j.exer.2022.109344_bib41","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0014-5793(98)01683-4","article-title":"Classical late infantile neuronal ceroid lipofuscinosis fibroblasts are deficient in lysosomal tripeptidyl peptidase I","volume":"443","author":"Vines","year":"1999","journal-title":"FEBS Lett."},{"key":"10.1016\/j.exer.2022.109344_bib42","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.ymgme.2011.06.018","article-title":"Intrathecal tripeptidyl-peptidase 1 reduces lysosomal storage in a canine model of late infantile neuronal ceroid lipofuscinosis","volume":"104","author":"Vuillemenot","year":"2011","journal-title":"Mol. Genet. Metabol."},{"key":"10.1016\/j.exer.2022.109344_bib43","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.ymgme.2014.09.004","article-title":"Nonclinical evaluation of CNS-administered TPP1 enzyme replacement in canine CLN2 neuronal ceroid lipofuscinosis","volume":"114","author":"Vuillemenot","year":"2015","journal-title":"Mol. Genet. Metabol."},{"key":"10.1016\/j.exer.2022.109344_bib44","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1016\/j.bbadis.2013.03.017","article-title":"Genetic basis and phenotypic correlations of the neuronal ceroid lipofusinoses","volume":"1832","author":"Warrier","year":"2013","journal-title":"Biochim. Biophys. Acta, Mol. Basis Dis."},{"key":"10.1016\/j.exer.2022.109344_bib45","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.exer.2016.03.023","article-title":"Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease","volume":"146","author":"Whiting","year":"2016","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109344_bib46","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.exer.2013.10.006","article-title":"Pupillary light reflex deficits in a canine model of late infantile neuronal ceroid lipofuscinosis","volume":"116","author":"Whiting","year":"2013","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109344_bib47","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2020.108130","article-title":"Intravitreal enzyme replacement preserves retinal structure and function in canine CLN2 neuronal ceroid lipofuscinosis","volume":"197","author":"Whiting","year":"2020","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109344_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2020.108130","article-title":"Intravitreal enzyme replacement inhibits progression of retinal degeneration in canine CLN2 neuronal ceroid lipofuscinosis","volume":"197","author":"Whiting","year":"2020","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109344_bib49","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1212\/01.wnl.0000267885.47092.40","article-title":"Neurological deterioration in late infantile neuronal ceroid lipofuscinosis","volume":"69","author":"Worgall","year":"2007","journal-title":"Neurology"},{"key":"10.1016\/j.exer.2022.109344_bib50","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1167\/iovs.10-6250","article-title":"Intravitreal injection of AAV2 transduces macaque inner retina","volume":"52","author":"Yin","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."}],"container-title":["Experimental Eye Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483522004250?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483522004250?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T05:23:43Z","timestamp":1758000223000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014483522004250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":50,"alternative-id":["S0014483522004250"],"URL":"https:\/\/doi.org\/10.1016\/j.exer.2022.109344","relation":{},"ISSN":["0014-4835"],"issn-type":[{"value":"0014-4835","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Intravitreal gene therapy preserves retinal function in a canine model of CLN2 neuronal ceroid lipofuscinosis","name":"articletitle","label":"Article Title"},{"value":"Experimental Eye Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exer.2022.109344","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"109344"}}