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Bone marrow-derived endothelial progenitor cells (EPCs) contribute to pathologic angiogenesis. Gene expression profiles downloaded from the eyeIntegration v1.0 database for healthy retinas and retinas from patients with neovascular AMD identified significantly higher levels of EPC-specific markers (CD34, CD133) and blood vessel markers (CD31, VEGF) in the neovascular AMD retinas compared with healthy retinas. Melatonin is a hormone that is mainly secreted by the pineal gland, and is also produced in the retina. Whether melatonin affects vascular endothelial growth factor (VEGF)-induced EPC angiogenesis in neovascular AMD is unknown. Our study revealed that melatonin inhibits VEGF-induced stimulation of EPC migration and tube formation. By directly binding with the VEGFR2 extracellular domain, melatonin significantly and dose-dependently inhibited VEGF-induced PDGF-BB expression and angiogenesis in EPCs via c-Src and FAK, NF-\u03baB and AP-1 signaling. The corneal alkali burn model demonstrated that melatonin markedly inhibited EPC angiogenesis and neovascular AMD. Melatonin appears promising for reducing EPC angiogenesis in neovascular AMD.<\/jats:p>","DOI":"10.3390\/cells12050799","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T06:29:06Z","timestamp":1678084146000},"page":"799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Melatonin Inhibits VEGF-Induced Endothelial Progenitor Cell Angiogenesis in Neovascular Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"12","author":[{"given":"Liang-Wei","family":"Lin","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 403433, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7522-6352","authenticated-orcid":false,"given":"Shih-Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan"},{"name":"Institute of Biomedical Sciences, Mackay Medical College, New Taipei City 25245, Taiwan"},{"name":"School of Pharmacy, College of Pharmacy, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6467-8716","authenticated-orcid":false,"given":"Wei-Chien","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 403433, Taiwan"},{"name":"Drug Development Center, China Medical University, Taichung 403433, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung 40354, Taiwan"},{"name":"Research Center for Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung 403433, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh 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Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s10456-019-09689-7","article-title":"Role of melatonin in controlling angiogenesis under physiological and pathological conditions","volume":"23","author":"Ma","year":"2019","journal-title":"Angiogenesis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1159\/000518822","article-title":"Global Incidence, Progression, and Risk Factors of Age-Related Macular Degeneration and Projection of Disease Statistics in 30 Years: A Modeling Study","volume":"68","author":"Wang","year":"2021","journal-title":"Gerontology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Patel, P., and Sheth, V. 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