{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T13:49:36Z","timestamp":1782481776289,"version":"3.54.5"},"reference-count":57,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research to Prevent Blindness to the Department of Ophthalmology and Visual Sciences"},{"DOI":"10.13039\/100013779","name":"Retina Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013779","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Arthur and Nancy Nesbit AMD Fund"},{"DOI":"10.13039\/100008097","name":"Edward N. & Della L. Thome Memorial Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008097","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Carl Marshall Reeves & Mildred Almen Reeves Foundation"},{"name":"Pat and Jay Smith AMD Innovation Fund"},{"DOI":"10.13039\/100000053","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 EY016665"],"award-info":[{"award-number":["P30 EY016665"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA014520"],"award-info":[{"award-number":["P30 CA014520"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY034646"],"award-info":[{"award-number":["EY034646"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY030076"],"award-info":[{"award-number":["EY030076"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Aging reduces the tissue regenerative capacity, promotes chronic inflammation, and contributes to neurodegenerative diseases, including age-related macular degeneration (AMD). AMD is a leading cause of vision loss in older adults and manifests as dry (atrophic) or wet (neovascular) disease. Although dry AMD is more prevalent, neovascular AMD (nAMD) causes the most severe vision impairment and remains a major public health burden. Oxidative stress-mediated inflammation and dysfunction of retinal pigment epithelium (RPE) cells and choriocapillaris drive early AMD. Neovascular AMD is marked by pathologic choroidal neovascularization (CNV), driven largely by dysregulated VEGF signaling. Anti-VEGF therapies are the current standard of care for nAMD but require frequent intravitreal injections, carry procedure-related risks, and are ineffective in a substantial subset of patients, underscoring the need for new therapeutic approaches. Caffeine, a widely consumed and well-tolerated adenosine receptor antagonist, has emerging relevance in vascular regulation and inflammatory signaling. Extracellular ATP and its metabolites, including adenosine, accumulate under stress and act through purinergic receptors to influence angioinflammatory processes. We recently showed that systemic caffeine administration suppressed CNV in vivo, an effect partly reproduced by the adenosine receptor A2A antagonist Istradefylline. Here, we investigated the cell-autonomous effects of caffeine on mouse choroidal endothelial cells, focusing on its role as an adenosine receptor antagonist and its potential to inhibit pathological neovascularization.<\/jats:p>","DOI":"10.3390\/cells15010087","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T16:07:07Z","timestamp":1767629227000},"page":"87","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Caffeine Mitigates Adenosine-Mediated Angiogenic Properties of Choroidal Endothelial Cells Through Antagonism of A1 Adenosine Receptor and PI3K-AKT Axis"],"prefix":"10.3390","volume":"15","author":[{"given":"SunYoung","family":"Park","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Seok","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Sorenson","sequence":"additional","affiliation":[{"name":"McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2723-9217","authenticated-orcid":false,"given":"Nader","family":"Sheibani","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"},{"name":"Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110551","DOI":"10.1016\/j.exer.2025.110551","article-title":"Unveiling the link: Aging and its impact on ocular diseases","volume":"259","author":"Wang","year":"2025","journal-title":"Exp. 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