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We still need to deeply understand retinal angiogenesis's molecular mechanisms and identify potential alternate therapeutic targets. We used RNA sequencing (RNA\u2010seq) and found fibronectin (\n                    <jats:italic>FN1<\/jats:italic>\n                    ), an extracellular matrix protein, was significantly upregulated during retinal angiogenesis in the oxygen\u2010induced retinopathy (OIR) model. Employing a deep learning model (BioNet) to identify potential\n                    <jats:italic>FN1<\/jats:italic>\n                    inhibitors among FDA\u2010approved drugs, we discovered that melatonin effectively reduced\n                    <jats:italic>FN1<\/jats:italic>\n                    expression and inhibited VEGF\u2010induced angiogenesis by decreasing VEGFR2 phosphorylation. In\u00a0vivo, melatonin administration significantly reduced preretinal tufts in the OIR model while suppressing\n                    <jats:italic>FN1<\/jats:italic>\n                    expression and VEGFR2 activation. This study highlights the power of computer\u2010driven drug discovery, with BioNet successfully identifying melatonin as a potential therapeutic agent for retinal angiogenesis. The ability of melatonin to inhibit both\n                    <jats:italic>FN1<\/jats:italic>\n                    and VEGF signaling highlights the potential of integrating advanced computational methods with rigorous experimental validation to uncover novel therapies for complex diseases.\n                  <\/jats:p>","DOI":"10.1096\/fj.202500814rr","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T14:19:02Z","timestamp":1759241942000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Melatonin Alleviates Retina Angiogenesis by Targeting Fibronectin and the\n                    <scp>VEGF<\/scp>\n                    Pathway"],"prefix":"10.1096","volume":"39","author":[{"given":"Fang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Hunan Key Laboratory of Ophthalmology, Xiangya Hospital Central South University  Changsha 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