{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:02:28Z","timestamp":1791928948507,"version":"4.3.4"},"reference-count":44,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"8","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2026,7,22]]},"DOI":"10.1167\/iovs.67.8.48","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T14:30:36Z","timestamp":1784730636000},"page":"48","source":"Crossref","is-referenced-by-count":0,"title":["LAG3 Gene Therapy Attenuates Autoimmune Uveitis by Regulating the PI3K\/Akt Signaling Pathway"],"prefix":"10.1167","volume":"67","author":[{"given":"Liu","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiujin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Su","sequence":"additional","affiliation":[{"name":"Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Du","sequence":"additional","affiliation":[{"name":"Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiang","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1007\/s00417-024-06422-z","article-title":"Epidemiology, clinical features, and classification of 3,404 patients with uveitis: Colombian Uveitis Multicenter Study (COL-UVEA)","volume":"262","author":"de-la-Torre","year":"2024","journal-title":"Graefes Arch Clin Exp Ophthalmol."},{"key":"bib2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12348-014-0017-9","article-title":"Autoimmune uveitis: a retrospective analysis of 104 patients from a tertiary reference center","volume":"4","author":"Prete","year":"2014","journal-title":"J Ophthalmic Inflamm Infect."},{"key":"bib3","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1080\/09273948.2024.2408411","article-title":"Epidemiology of intermediate uveitis","volume":"33","author":"Besagar","year":"2025","journal-title":"Ocul Immunol Inflamm."},{"key":"bib4","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1007\/s10792-021-01763-8","article-title":"New pharmacotherapy options for noninfectious posterior uveitis","volume":"41","author":"Pleyer","year":"2021","journal-title":"Int Ophthalmol."},{"key":"bib5","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/978-1-60761-720-4","article-title":"Rodent models of experimental autoimmune uveitis","volume":"900","author":"Agarwal","year":"2012","journal-title":"Methods Mol Biol"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"11513","DOI":"10.3390\/ijms252111513","article-title":"Enhanced ROS production and mitochondrial metabolic shifts in CD4+ T cells of an autoimmune uveitis model","volume":"25","author":"S\u00f6th","year":"2024","journal-title":"Int J Mol Sci"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1084\/jem.20071258","article-title":"Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category","volume":"205","author":"Luger","year":"2008","journal-title":"J Exp Med."},{"key":"bib8","doi-asserted-by":"publisher","first-page":"3338","DOI":"10.4049\/jimmunol.1004019","article-title":"Autoreactive memory CD4+ T lymphocytes that mediate chronic uveitis reside in the bone marrow through STAT3-dependent mechanisms","volume":"187","author":"Oh","year":"2011","journal-title":"J Immunol"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41590-022-01387-9","article-title":"TH17 cell heterogeneity and its role in tissue inflammation","volume":"24","author":"Schnell","year":"2023","journal-title":"Nat Immunol"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"5450","DOI":"10.4049\/jimmunol.172.9.5450","article-title":"Lymphocyte activation gene-3 (CD223) regulates the size of the expanding T cell population following antigen activation in vivo","volume":"172","author":"Workman","year":"2004","journal-title":"J Immunol"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"107241","DOI":"10.1016\/j.jbc.2024.107241","article-title":"The immune checkpoint receptor LAG3: structure, function, and target for cancer immunotherapy","volume":"300","author":"Mariuzza","year":"2024","journal-title":"J Biol Chem."},{"key":"bib12","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1111\/imr.12519","article-title":"LAG3 (CD223) as a cancer immunotherapy target","volume":"276","author":"Andrews","year":"2017","journal-title":"Immunol Rev"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"102504","DOI":"10.1016\/j.jaut.2020.102504","article-title":"LAG3 (CD223) and autoimmunity: emerging evidence","volume":"112","author":"Hu","year":"2020","journal-title":"J Automimmun"},{"key":"bib14","first-page":"62","article-title":"Targeting T cell checkpoints 41BB and LAG3 and myeloid cell CXCR1\/CXCR2 results in antitumor immunity and durable response in pancreatic cancer","volume":"4","author":"Gulhati","year":"2023","journal-title":"Nat Cancer"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1056\/NEJMoa2109970","article-title":"Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma","volume":"386","author":"Tawbi","year":"2022","journal-title":"N Engl J Med"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"4373","DOI":"10.1016\/j.cell.2024.06.036","article-title":"Blockade of LAG-3 and PD-1 leads to co-expression of cytotoxic and exhaustion gene modules in CD8+ T cells to promote antitumor immunity","volume":"187","author":"Cillo","year":"2024","journal-title":"Cell"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"e104484","DOI":"10.1371\/journal.pone.0104484","article-title":"Lymphocyte activation gene-3 (LAG-3) negatively regulates environmentally-induced autoimmunity","volume":"9","author":"Jha","year":"2014","journal-title":"PLoS One"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"11639","DOI":"10.1038\/ncomms11639","article-title":"Gut environment-induced intraepithelial autoreactive CD4+ T cells suppress central nervous system autoimmunity via LAG-3","volume":"7","author":"Kadowaki","year":"2016","journal-title":"Nat Commun"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.4049\/jimmunol.1800898","article-title":"Cutting edge: IL-27 attenuates autoimmune neuroinflammation via regulatory T cell\/Lag3-dependent but IL-10-independent mechanisms in vivo","volume":"202","author":"Kim","year":"2019","journal-title":"J Immunol"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.1167\/iovs.07-0868","article-title":"Repertoire analysis and new pathogenic epitopes of IRBP in C57BL\/6 (H-2b) and B10.RIII (H-2r) mice","volume":"49","author":"Cortes","year":"2008","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib21","first-page":"21","article-title":"Muscone attenuates uveitis through the PI3K\/Akt signaling pathway","volume":"66","author":"Liu","year":"2025","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"31912","DOI":"10.1038\/srep31912","article-title":"AAV8-mediated angiotensin-converting enzyme 2 gene delivery prevents experimental autoimmune uveitis by regulating MAPK, NF-?B and STAT3 pathways","volume":"6","author":"Qiu","year":"2016","journal-title":"Sci Rep"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1189\/jlb.1102574","article-title":"Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation","volume":"74","author":"Streilein","year":"2003","journal-title":"J Leukoc Biol"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1111\/febs.16330","article-title":"The blood\u2013retina barrier in health and disease","volume":"290","author":"O'Leary","year":"2023","journal-title":"FEBS J"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s10792-025-03870-2","article-title":"The blood\u2013retinal barrier in ocular pathologies: an updated narrative review","volume":"46","author":"Hang","year":"2025","journal-title":"Int Ophthalmol"},{"issue":"6","key":"bib26","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.5301\/EJO.2010.6049","article-title":"Blood\u2013retinal barrier","volume":"21","author":"Cunha-Vaz","year":"2011","journal-title":"Eur J Ophthalmol"},{"key":"bib27","first-page":"33","article-title":"Distinct mechanisms of human retinal endothelial barrier modulation in vitro by mediators of diabetes and uveitis","volume":"12","author":"Rudraraju","year":"2021","journal-title":"Life (Basel)"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"1703382","DOI":"10.3389\/fimmu.2025.1703382","article-title":"Breach and restoration of retinal immune privilege: barrier failure, innate dysregulation, and adaptive autoimmunity","volume":"16","author":"Fan","year":"2025","journal-title":"Front Immunol"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"190724","DOI":"10.1155\/2010\/190724","article-title":"The retinal pigment epithelium: something more than a constituent of the blood\u2013retinal barrier\u2014implications for the pathogenesis of diabetic retinopathy","volume":"2010","author":"Sim\u00f3","year":"2010","journal-title":"J Biomed Biotechnol"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"211","DOI":"10.3390\/ijms21010211","article-title":"Tight junctions of the outer blood retina barrier","volume":"21","author":"Naylor","year":"2019","journal-title":"Int J Mol Sci"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/mi.2015.45","article-title":"An IL-27\/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy","volume":"9","author":"Do","year":"2016","journal-title":"Mucosal Immunol"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"688","DOI":"10.4049\/jimmunol.174.2.688","article-title":"Negative regulation of T cell homeostasis by lymphocyte activation gene-3 (CD223)","volume":"174","author":"Workman","year":"2005","journal-title":"J Immunol"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1084\/jem.20100466","article-title":"PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice","volume":"208","author":"Okazaki","year":"2011","journal-title":"J Exp Med"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"3493","DOI":"10.4049\/jimmunol.1100714","article-title":"Cutting edge: accelerated autoimmune diabetes in the absence of LAG-3","volume":"187","author":"Bettini","year":"2011","journal-title":"J Immunol"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"e005548","DOI":"10.1136\/jitc-2022-005548","article-title":"Deciphering molecular and cellular ex vivo responses to bispecific antibodies PD1-TIM3 and PD1-LAG3 in human tumors","volume":"10","author":"Natoli","year":"2022","journal-title":"J Immunother Cancer"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1080\/13816810.2018.1533027","article-title":"Gene therapy for RPE65-related retinal disease","volume":"39","author":"Miraldi Utz","year":"2018","journal-title":"Ophthalmic Genet"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1093\/jimmun\/vkaf120","article-title":"LAG3\u2013MHCII interaction induces a tight cell\u2013cell interface at the immunological synapse","volume":"214","author":"Wang","year":"2025","journal-title":"J Immunol"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1080\/15384101.2021.1924450","article-title":"Role of lncRNA XIST\/microRNA-19\/PTEN network in autophagy of nucleus pulposus cells in intervertebral disc degeneration via the PI3K\/Akt signaling pathway","volume":"20","author":"Chen","year":"2021","journal-title":"Cell Cycle"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1186\/s12967-025-06319-3","article-title":"Complement C3a promotes the formation of osteoclasts by inhibiting Sirt1 to activate the PI3K\/PDK1\/SGK3 pathway in patients with multiple myeloma","volume":"23","author":"Jiang","year":"2025","journal-title":"J Transl Med"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1158\/2159-8290.CD-20-1265","article-title":"Ontogeny and vulnerabilities of drug-tolerant persisters in HER2+ breast cancer","volume":"12","author":"Chang","year":"2022","journal-title":"Cancer Discov"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1007\/s10753-024-02099-y","article-title":"Methylprednisolone modulates the Tfr\/Tfh ratio in EAE-induced neuroinflammation through the PI3K\/AKT\/FoxO1 and PI3K\/AKT\/mTOR signalling pathways","volume":"48","author":"Wu","year":"2025","journal-title":"Inflammation"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1016\/j.fsi.2021.12.046","article-title":"PI3K\/AKT\/p53 pathway inhibits infectious spleen and kidney necrosis virus infection by regulating autophagy and immune responses","volume":"120","author":"Zhang","year":"2022","journal-title":"Fish Shellfish Immunol"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"112891","DOI":"10.1016\/j.intimp.2024.112891","article-title":"MIF aggravates experimental autoimmune prostatitis through activation of the NLRP3 inflammasome via the PI3K\/AKT pathway","volume":"141","author":"Zhang","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1385\/IR:31:1:47","article-title":"PI3K\/AKT signaling and systemic autoimmunity","volume":"31","author":"Patel","year":"2005","journal-title":"Immunol Res"}],"container-title":["Investigative Ophthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.67.8.48","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:32:20Z","timestamp":1791927140000},"score":1,"resource":{"primary":{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.67.8.48"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":44,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.67.8.48","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7,22]]}}}