{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:33:00Z","timestamp":1793161980338,"version":"4.5.0"},"reference-count":71,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"737","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,3,6]]},"abstract":"<jats:p>\n                    Anti\u2013vascular endothelial growth factor therapy has had a substantial impact on the treatment of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD), the leading cause of vision loss in older adults. Despite treatment, many patients with nAMD still develop severe and irreversible visual impairment because of the development of subretinal fibrosis. We recently reported the anti-inflammatory and antiangiogenic effects of inhibiting the gene encoding adenosine receptor 2A (\n                    <jats:italic>Adora2a<\/jats:italic>\n                    ), which has been implicated in cardiovascular disease. Here, using two mouse models of subretinal fibrosis (mice with laser injury\u2013induced CNV or mice with a deficiency in the very low\u2013density lipoprotein receptor), we found that deletion of\n                    <jats:italic>Adora2a<\/jats:italic>\n                    either globally or specifically in endothelial cells reduced subretinal fibrosis independently of angiogenesis. We showed that\n                    <jats:italic>Adora2a<\/jats:italic>\n                    -dependent endothelial-to-mesenchymal transition contributed to the development of subretinal fibrosis in mice with laser injury\u2013induced CNV. Deficiency of\n                    <jats:italic>Adora2a<\/jats:italic>\n                    in cultured mouse and human choroidal endothelial cells suppressed induction of the endothelial-to-mesenchymal transition. A metabolomics analysis of cultured human choroidal endothelial cells showed that\n                    <jats:italic>ADORA2A<\/jats:italic>\n                    knockdown with an siRNA reversed the increase in succinate because of decreased succinate dehydrogenase B expression under fibrotic conditions. Pharmacological inhibition of ADORA2A with a small-molecule KW6002 in both mouse models recapitulated the reduction in subretinal fibrosis observed in mice with genetic deletion of\n                    <jats:italic>Adora2a<\/jats:italic>\n                    . ADORA2A inhibition may be a therapeutic approach to treat subretinal fibrosis associated with nAMD.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adk3868","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T13:58:10Z","timestamp":1709733490000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":25,"title":["Inactivation of adenosine receptor 2A suppresses endothelial-to-mesenchymal transition and inhibits subretinal fibrosis in mice"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5582-3771","authenticated-orcid":true,"given":"Qiuhua","family":"Yang","sequence":"first","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfeng","family":"Cai","sequence":"additional","affiliation":[{"name":"Vascular Biology Center, 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Yang Y. Cai Q. Ma A. Xiong P. Xu Z. Zhang J. Xu Y. Zhou Z. Liu D. Zhao J. Asara W. Li H. Shi R. Caldwell A. Akrit Y. Huo. Inactivation of adenosine receptor 2A suppresses endothelial-to-mesenchymal transition and inhibits subretinal fibrosis in mice [Dataset]. 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