{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T08:42:10Z","timestamp":1793954530766,"version":"4.8.0"},"reference-count":123,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"unspecified","delay-in-days":105,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Expert Rev. Mol. Med."],"published-print":{"date-parts":[[2024]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t  <jats:p>Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and mechanisms but share a multifactorial and complex nature, making their management challenging and burdensome for patients and clinicians. Furthermore, the lack of symptoms in the early stages of glaucoma and the diverse aetiology of uveitis hinder timely and accurate diagnoses, which are a cause of poor visual outcomes under both conditions. Although current treatment is effective in most cases, it is often associated with low patient adherence and adverse events, which directly impact the overall therapeutic success. Therefore, long-lasting alternatives with improved safety and efficacy are needed. Gene therapy, particularly utilising adeno-associated virus (AAV) vectors, has emerged as a promising approach to address unmet needs in these diseases. Engineered capsids with enhanced tropism and lower immunogenicity have been proposed, along with constructs designed for targeted and controlled expression. Additionally, several pathways implicated in the pathogenesis of these conditions have been targeted with single or multigene expression cassettes, gene editing and silencing approaches. This review discusses strategies employed in AAV-based gene therapies for glaucoma and non-infectious uveitis and provides an overview of current progress and future directions.<\/jats:p>","DOI":"10.1017\/erm.2024.4","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T09:43:51Z","timestamp":1713174231000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":15,"title":["AAV-mediated gene therapies for glaucoma and uveitis: are we there yet?"],"prefix":"10.1017","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3604-8757","authenticated-orcid":false,"given":"Brenda","family":"Castro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3608-7542","authenticated-orcid":false,"given":"Jason C.","family":"Steel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6933-9991","authenticated-orcid":false,"given":"Christopher J.","family":"Layton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2024,4,15]]},"reference":[{"key":"S1462399424000048_ref76","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.608377"},{"key":"S1462399424000048_ref98","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17703"},{"key":"S1462399424000048_ref104","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.03.012"},{"key":"S1462399424000048_ref19","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2019.1663385"},{"key":"S1462399424000048_ref108","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.62.2.41"},{"key":"S1462399424000048_ref118","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.08.028"},{"key":"S1462399424000048_ref81","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S180580"},{"key":"S1462399424000048_ref26","doi-asserted-by":"publisher","DOI":"10.1111\/brv.12718"},{"key":"S1462399424000048_ref59","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-15008"},{"key":"S1462399424000048_ref54","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-8484"},{"key":"S1462399424000048_ref111","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.269"},{"key":"S1462399424000048_ref33","first-page":"1048","article-title":"Bcl-2, Bcl-xL, and p-AKT are involved in neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma","volume":"22","author":"Phatak","year":"2016","journal-title":"Molecular Vision"},{"key":"S1462399424000048_ref10","doi-asserted-by":"publisher","DOI":"10.1007\/s10792-020-01496-0"},{"key":"S1462399424000048_ref78","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.04.003"},{"key":"S1462399424000048_ref40","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.4103\/ijo.IJO_3117_20","article-title":"Gene therapy in retinal diseases: a review","volume":"69","author":"Dhurandhar","year":"2021","journal-title":"Indian Journal of Ophthalmology"},{"key":"S1462399424000048_ref7","doi-asserted-by":"publisher","DOI":"10.3390\/nu14030534"},{"key":"S1462399424000048_ref115","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33745-4"},{"key":"S1462399424000048_ref45","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a017244"},{"key":"S1462399424000048_ref58","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.599373"},{"key":"S1462399424000048_ref60","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04068-x"},{"key":"S1462399424000048_ref24","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2021.104329"},{"key":"S1462399424000048_ref119","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.13434"},{"key":"S1462399424000048_ref53","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-1332"},{"key":"S1462399424000048_ref44","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-66350-w"},{"key":"S1462399424000048_ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2019.06.004"},{"key":"S1462399424000048_ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108506"},{"key":"S1462399424000048_ref120","first-page":"699","article-title":"Human leukocyte antigen-G expression and polymorphisms promote cancer development and guide cancer diagnosis\/treatment","volume":"15","author":"Zhang","year":"2018","journal-title":"Oncology Letters"},{"key":"S1462399424000048_ref64","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2019.11.017"},{"key":"S1462399424000048_ref63","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2017.85"},{"key":"S1462399424000048_ref86","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.13511"},{"key":"S1462399424000048_ref90","doi-asserted-by":"publisher","DOI":"10.1016\/j.pop.2015.05.003"},{"key":"S1462399424000048_ref30","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.63.2.5"},{"key":"S1462399424000048_ref50","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6701588"},{"key":"S1462399424000048_ref88","volume-title":"StatPearls","author":"Duplechain","year":"2023"},{"key":"S1462399424000048_ref122","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2020.043"},{"key":"S1462399424000048_ref21","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2017.00494"},{"key":"S1462399424000048_ref57","doi-asserted-by":"publisher","DOI":"10.3390\/app10249015"},{"key":"S1462399424000048_ref85","doi-asserted-by":"publisher","DOI":"10.1080\/09273940801899822"},{"key":"S1462399424000048_ref121","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-020-0162-8"},{"key":"S1462399424000048_ref8","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9483e"},{"key":"S1462399424000048_ref71","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.879957"},{"key":"S1462399424000048_ref103","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10184133"},{"key":"S1462399424000048_ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2021.12.003"},{"key":"S1462399424000048_ref51","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2023.101225"},{"key":"S1462399424000048_ref4","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2022.2104637"},{"key":"S1462399424000048_ref47","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/742792"},{"key":"S1462399424000048_ref74","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1679197"},{"key":"S1462399424000048_ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2021.06.017"},{"key":"S1462399424000048_ref72","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adf6537"},{"key":"S1462399424000048_ref116","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.01.018"},{"key":"S1462399424000048_ref83","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2016.1196713"},{"key":"S1462399424000048_ref70","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-020-0862-8"},{"key":"S1462399424000048_ref91","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108618"},{"key":"S1462399424000048_ref123","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2017.179"},{"key":"S1462399424000048_ref109","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.675897"},{"key":"S1462399424000048_ref6","doi-asserted-by":"publisher","DOI":"10.1038\/s41435-022-00168-6"},{"key":"S1462399424000048_ref18","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073465"},{"key":"S1462399424000048_ref84","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.ajo.2005.03.057","article-title":"Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop","volume":"140","author":"Jabs","year":"2005","journal-title":"American Journal of Ophthalmology"},{"key":"S1462399424000048_ref92","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2019.1692810"},{"key":"S1462399424000048_ref56","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176262"},{"key":"S1462399424000048_ref99","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-59666-0"},{"key":"S1462399424000048_ref67","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2019.06.009"},{"key":"S1462399424000048_ref11","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-018-2557-4"},{"key":"S1462399424000048_ref29","first-page":"799","article-title":"Adeno-associated virus mediated SOD gene therapy protects the retinal ganglion cells from chronic intraocular pressure elevation induced injury via attenuating oxidative stress and improving mitochondrial dysfunction in a rat model","volume":"8","author":"Jiang","year":"2016","journal-title":"American Journal of Translational Research"},{"key":"S1462399424000048_ref62","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2017.04.003"},{"key":"S1462399424000048_ref46","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens11070756"},{"key":"S1462399424000048_ref107","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.10.4.3"},{"key":"S1462399424000048_ref35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0270972"},{"key":"S1462399424000048_ref16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.623725"},{"key":"S1462399424000048_ref75","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/671417"},{"key":"S1462399424000048_ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cobme.2021.100353"},{"key":"S1462399424000048_ref61","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2016.08.003"},{"key":"S1462399424000048_ref65","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.04.014"},{"key":"S1462399424000048_ref80","doi-asserted-by":"publisher","DOI":"10.1177\/1120672119899379"},{"key":"S1462399424000048_ref97","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2022.101110"},{"key":"S1462399424000048_ref87","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m4979"},{"key":"S1462399424000048_ref36","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13086"},{"key":"S1462399424000048_ref89","doi-asserted-by":"publisher","DOI":"10.1080\/09286586.2020.1856385"},{"key":"S1462399424000048_ref110","doi-asserted-by":"publisher","DOI":"10.3390\/cells11121881"},{"key":"S1462399424000048_ref20","doi-asserted-by":"publisher","DOI":"10.1111\/vop.12858"},{"key":"S1462399424000048_ref43","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31469-1"},{"key":"S1462399424000048_ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(20)30489-7"},{"key":"S1462399424000048_ref38","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8122082"},{"key":"S1462399424000048_ref106","unstructured":"106. Silvent, J (2022) Janssen Announces Late-Breaking Data from Two Gene Therapy Programs at the American Academy of Ophthalmology 2022 Annual Meeting. Available at https:\/\/www.jnj.com\/press-releases\/janssen-announces-late-breaking-data-from-two-gene-therapy-programs-at-the-american-academy-of-ophthalmology-2022-annual-meeting"},{"key":"S1462399424000048_ref73","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx028"},{"key":"S1462399424000048_ref105","first-page":"16","article-title":"CLINICAL TRIAL DOWNLOAD: data on a gene therapy for dry and wet AMD A phase 1 clinical trial program is targeting both disease states","volume":"17","author":"Dugel","year":"2020","journal-title":"Retinal Physician"},{"key":"S1462399424000048_ref17","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-021-01766-w"},{"key":"S1462399424000048_ref79","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2015.10.028"},{"key":"S1462399424000048_ref96","doi-asserted-by":"publisher","DOI":"10.1097\/IIO.0000000000000366"},{"key":"S1462399424000048_ref94","doi-asserted-by":"publisher","DOI":"10.3390\/cells10020396"},{"key":"S1462399424000048_ref32","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1041-8"},{"key":"S1462399424000048_ref42","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-053805"},{"key":"S1462399424000048_ref117","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0205-4"},{"key":"S1462399424000048_ref95","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.30"},{"key":"S1462399424000048_ref15","first-page":"21","article-title":"Gene therapy for uveitis","volume":"61","author":"Bordet","year":"2021","journal-title":"International Ophthalmology Clinics"},{"key":"S1462399424000048_ref27","first-page":"73","article-title":"AAV-based strategies for treatment of retinal and choroidal vascular diseases: advances in age-related macular degeneration and diabetic retinopathy therapies","volume":"1","author":"Castro","year":"2023","journal-title":"Biodrugs"},{"key":"S1462399424000048_ref66","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2014.05.018"},{"key":"S1462399424000048_ref102","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2015.10.056"},{"key":"S1462399424000048_ref49","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2023.101218"},{"key":"S1462399424000048_ref25","doi-asserted-by":"publisher","DOI":"10.1097\/ICU.0000000000000562"},{"key":"S1462399424000048_ref101","doi-asserted-by":"publisher","DOI":"10.1177\/112067210701700611"},{"key":"S1462399424000048_ref9","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1200427"},{"key":"S1462399424000048_ref113","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.846782"},{"key":"S1462399424000048_ref77","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.107853"},{"key":"S1462399424000048_ref34","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-56462-3"},{"key":"S1462399424000048_ref2","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.14035"},{"key":"S1462399424000048_ref52","first-page":"816","article-title":"Tyrosine triple mutated AAV2-BDNF gene therapy in a rat model of transient IOP elevation","volume":"22","author":"Igarashi","year":"2016","journal-title":"Molecular Vision"},{"key":"S1462399424000048_ref112","doi-asserted-by":"publisher","DOI":"10.1038\/srep31912"},{"key":"S1462399424000048_ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2021.01.012"},{"key":"S1462399424000048_ref22","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.612422"},{"key":"S1462399424000048_ref41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ogla.2020.12.007"},{"key":"S1462399424000048_ref114","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.01.023"},{"key":"S1462399424000048_ref37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.736261"},{"key":"S1462399424000048_ref48","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3192"},{"key":"S1462399424000048_ref82","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2014.01.006"},{"key":"S1462399424000048_ref69","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.12.012"},{"key":"S1462399424000048_ref93","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0502-y"},{"key":"S1462399424000048_ref39","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.795010"},{"key":"S1462399424000048_ref3","doi-asserted-by":"crossref","first-page":"9","DOI":"10.5005\/jp-journals-10078-1242","article-title":"Evaluation of vision-related quality of life in patients with glaucoma: a hospital-based study","volume":"13","author":"Dhawan","year":"2019","journal-title":"Journal of Current Glaucoma Practice"},{"key":"S1462399424000048_ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.106129"},{"key":"S1462399424000048_ref55","first-page":"409","article-title":"Tyrosine triple mutated AAV2-BDNF gene therapy in an inner retinal injury model induced by intravitreal injection of N-methyl-d-aspartate (NMDA)","volume":"26","author":"Shiozawa","year":"2020","journal-title":"Molecular Vision"},{"key":"S1462399424000048_ref100","doi-asserted-by":"publisher","DOI":"10.1007\/s40135-016-0090-3"},{"key":"S1462399424000048_ref68","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12030269"}],"container-title":["Expert Reviews in Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1462399424000048","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T09:44:03Z","timestamp":1713174243000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1462399424000048\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024]]},"references-count":123,"alternative-id":["S1462399424000048"],"URL":"https:\/\/doi.org\/10.1017\/erm.2024.4","relation":{},"ISSN":["1462-3994"],"issn-type":[{"value":"1462-3994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024]]},"assertion":[{"value":"Copyright \u00a9 The Author(s), 2024. Published by Cambridge University Press","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http:\/\/creativecommons.org\/licenses\/by\/4.0\/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}],"article-number":"e9"}}