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Neuronal\/glial-vascular interactions influence the release of angiogenic and neurotrophic factors. We hypothesized that botulinum neurotoxin serotype A (BoNT\/A) modulates pathological endothelial cell proliferation through glial cell activation and growth factor release.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A laser-induced choroidal NV (CNV) was employed to investigate the anti-angiogenic effects of BoNT\/A. Fundus fluorescence angiography, immunohistochemistry, and real-time PCR were used to assess BoNT\/A efficacy in inhibiting CNV and the molecular mechanisms underlying this inhibition. Neuronal and glial suppressor of cytokine signaling 3 (SOCS3) deficient mice were used to investigate the molecular mechanisms of BoNT\/A in inhibiting CNV via SOCS3.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Findings<\/jats:title>\n                <jats:p>In laser-induced CNV mice with intravitreal BoNT\/A treatment, CNV lesions decreased\u2009&gt;\u200930%; vascular leakage and retinal glial activation were suppressed; and <jats:italic>Socs3<\/jats:italic> mRNA expression was induced while vascular endothelial growth factor A (<jats:italic>Vegfa<\/jats:italic>) mRNA expression was suppressed. The protective effects of BoNT\/A on CNV development were diminished in mice lacking neuronal\/glial SOCS3.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>BoNT\/A suppressed laser-induced CNV and glial cell activation, in part through SOCS3 induction in neuronal\/glial cells. BoNT\/A treatment led to a decrease of pro-angiogenic factors, including VEGFA, highlighting the potential of BoNT\/A as a therapeutic intervention for pathological angiogenesis in retinopathies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10456-024-09935-7","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T15:04:21Z","timestamp":1719414261000},"page":"753-764","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Botulinum neurotoxin serotype A inhibited ocular angiogenesis through modulating glial activation via SOCS3"],"prefix":"10.1007","volume":"27","author":[{"given":"Austin T.","family":"Gregg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianxi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manon","family":"Szczepan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enton","family":"Lam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitomi","family":"Yagi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Neilsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lois E. 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