{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:41:48Z","timestamp":1770140508073,"version":"3.49.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T00:00:00Z","timestamp":1660780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011485","name":"North Carolina Translational and Clinical Sciences Institute, University of North Carolina at Chapel Hill","doi-asserted-by":"publisher","award":["550KR211915"],"award-info":[{"award-number":["550KR211915"]}],"id":[{"id":"10.13039\/100011485","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Equine recurrent uveitis (ERU) is a spontaneous, painful, and vision threatening disease affecting up to 25% of equine populations worldwide. Current treatments of ERU are non-specific and have many side effects which limits them to short-term use. In order to develop an effective therapy for ERU, we investigated the use of adeno-associated virus (AAV) gene therapy, exploiting a natural immune tolerance mechanism induced by equine interleukin-10 (Equine-IL10). The purpose of this study was to evaluate the therapeutic efficacy of a single intravitreal (IVT) dose of AAV8-Equine-IL10 gene therapy for inhibition of experimental autoimmune uveitis (EAU) in rats. Each rat was dosed intravitreally (IVT) in both eyes with either balanced salt solution (BSS) (control; n = 4), AAV8-Equine-IL10 at a low dose (2.4x10<jats:sup>9<\/jats:sup>vg; n = 5) or high dose (2.4x10<jats:sup>10<\/jats:sup>vg; n = 5). EAU was induced in all groups of rats 7 days after IVT injections and euthanized 21 days post-injection. Ophthalmic examination and aqueous humor (AH) cell counts were recorded with the observer blinded to the treatment groups. Histopathology and qPCR were performed on selected ocular tissues. Data presented herein demonstrate that AAV8-Equine-IL10 treated rats exhibited a significant decrease in clinical inflammatory scores and AH cell counts compared to BSS-treated EAU eyes on days 10, 12 and 14 post EAU induction at both administered vector doses. Mean cellular histologic infiltrative scores were also significantly less in AAV8-Equine-IL10 dosed rats compared to the BSS group. Intravitreal injection of AAV8-Equine-IL10 resulted in Equine-IL10 cDNA expression in the ciliary body, retina, cornea, and optic nerve in a dose-dependent manner. A single IVT injection of AAV8-Equine-IL10 appeared to be well-tolerated and inhibited EAU even at the lowest administered dose. These results demonstrate safety and efficacy of AAV8-Equine-IL10 to prevent EAU and support continued exploration of AAV gene therapy for the treatment of equine and perhaps human recurrent uveitis.<\/jats:p>","DOI":"10.1371\/journal.pone.0270972","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T17:50:55Z","timestamp":1660845055000},"page":"e0270972","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Inhibition of experimental autoimmune uveitis by intravitreal AAV-Equine-IL10 gene therapy"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4671-8072","authenticated-orcid":true,"given":"Elizabeth","family":"Crabtree","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katy","family":"Uribe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara M.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darby","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacklyn H.","family":"Salmon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacquelyn J.","family":"Bower","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liujiang","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prabhakar","family":"Bastola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew L.","family":"Hirsch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7771-9166","authenticated-orcid":true,"given":"Brian C.","family":"Gilger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,8,18]]},"reference":[{"issue":"3","key":"pone.0270972.ref001","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/evj.12451","article-title":"Prognosis and impact of equine recurrent uveitis","volume":"48","author":"JC Gerding","year":"2016","journal-title":"Equine Veterinary Journal"},{"issue":"17\u201318","key":"pone.0270972.ref002","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.cca.2010.04.017","article-title":"Uveitis: Mechanisms and recent advances in therapy","volume":"411","author":"A Srivastava","year":"2010","journal-title":"Clinica Chimica Acta"},{"key":"pone.0270972.ref003","article-title":"Immune Relevant Models for Ocular Inflammatory Diseases.","author":"BC Gilger","year":"2018","journal-title":"ILAR Journal"},{"issue":"3","key":"pone.0270972.ref004","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/age.12129","article-title":"Genetic risk factors for insidious equine recurrent uveitis in Appaloosa horses","volume":"45","author":"KL Fritz","year":"2014","journal-title":"Animal Genetics"},{"issue":"January","key":"pone.0270972.ref005","first-page":"1","article-title":"Risk factors for equine recurrent uveitis in a population of Appaloosa horses in western Canada","volume":"23","author":"LS Sandmeyer","year":"2020","journal-title":"Veterinary ophthalmology"},{"key":"pone.0270972.ref006","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.cimid.2015.11.004","article-title":"Multiple etiologies of equine recurrent uveitis\u2014A natural model for human autoimmune uveitis: A brief review","volume":"44","author":"L Witkowski","year":"2016","journal-title":"Comparative Immunology, Microbiology and Infectious Diseases"},{"issue":"SUPPL.1","key":"pone.0270972.ref007","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1463-5224.2008.00625.x","article-title":"Ocular immunology in equine recurrent uveitis","volume":"11","author":"CA Deeg","year":"2008","journal-title":"Veterinary Ophthalmology"},{"key":"pone.0270972.ref008","unstructured":"English, Robert, Gilger B. 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