{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:24:17Z","timestamp":1787757857921,"version":"build-2784847793"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>To evaluate the causal effects of coffee-related circulating biomarkers on myopia and to nominate plausible biological mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Leveraging a two-sample Mendelian randomization (MR) framework, this study integrated in silico network pharmacology, gene-level MR, and computational structure-based modeling to investigate the relationship.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We performed MR for 11 coffee-associated biomarkers using summary-level genome-wide association data. Predicted targets of 7-methylxanthine (7-MX) were intersected with myopia-associated genes to construct a protein\u2013protein interaction network, identify hub genes, and conduct GO\/KEGG enrichment. Gene-level MR was applied to prioritize causal candidates. The interaction between 7-MX and the key target was evaluated by molecular docking and explored by molecular dynamics (MD) simulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Genetically predicted 7-MX showed a protective association with myopia (OR 0.77; 95% CI 0.62\u20130.95;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.014), whereas other biomarkers were null. Overlapping genes were enriched in angiogenic and signaling pathways, including VEGF and PI3K\u2013Akt. Among hub genes, EPHB4 was prioritized; higher genetically predicted EPHB4 expression was associated with a lower myopia risk (OR 0.90; 95% CI 0.84\u20130.97;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.005). Docking indicated stable 7-MX binding within the EPHB4 ATP pocket, which was supported by MD trajectories.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Convergent genetic, network, and computational evidence suggests a protective role of 7-MX against myopia, potentially mediated by direct engagement of EPHB4 and modulation of angiogenic signaling. These findings are hypothesis-generating and warrant replication in larger genome-wide association studies and functional validation in ocular models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijo.ijo_2539_25","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T10:00:15Z","timestamp":1770804015000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Genetic and network evidence that coffee-derived 7-methylxanthine mitigates myopia via the EPHB4 axis"],"prefix":"10.4103","author":[{"given":"Mozi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shengzhou Shen\u2019s Eye Hospital, Shengzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,2,11]]},"container-title":["Indian Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/IJO.IJO_2539_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:55:29Z","timestamp":1787756129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/IJO.IJO_2539_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":0,"URL":"https:\/\/doi.org\/10.4103\/ijo.ijo_2539_25","relation":{},"ISSN":["0301-4738","1998-3689"],"issn-type":[{"value":"0301-4738","type":"print"},{"value":"1998-3689","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,11]]},"assertion":[{"value":"2025-10-06","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-29","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}