{"doi":"10.1007/s10456-024-09935-7","title":"Botulinum neurotoxin serotype A inhibited ocular angiogenesis through modulating glial activation via SOCS3","abstract":"BACKGROUND: Pathological angiogenesis causes significant vision loss in neovascular age-related macular degeneration and other retinopathies with neovascularization (NV). 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. METHODS: 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. FINDINGS: In laser-induced CNV mice with intravitreal BoNT/A treatment, CNV lesions decreased > 30%; vascular leakage and retinal glial activation were suppressed; and Socs3 mRNA expression was induced while vascular endothelial growth factor A (Vegfa) mRNA expression was suppressed. The protective effects of BoNT/A on CNV development were diminished in mice lacking neuronal/glial SOCS3. CONCLUSION: 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.","journal":"Angiogenesis","year":2024,"id":480522,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9582,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":365109,"name":"Tianxi Wang","orcid":"0009-0000-9065-4400","position":1,"is_corresponding":false},{"id":1255572,"name":"Manon Szczepan","orcid":"0000-0003-1438-8504","position":2,"is_corresponding":false},{"id":725343,"name":"Enton Lam","orcid":null,"position":3,"is_corresponding":false},{"id":1075891,"name":"Hitomi Yagi","orcid":"0000-0002-5199-1970","position":4,"is_corresponding":false},{"id":1076355,"name":"Katherine Neilsen","orcid":null,"position":5,"is_corresponding":false},{"id":382323,"name":"Xingyan Wang","orcid":null,"position":6,"is_corresponding":false},{"id":90501,"name":"Lois E. H. Smith","orcid":"0000-0001-7644-6410","position":7,"is_corresponding":false},{"id":250314,"name":"Ye Sun","orcid":"0000-0002-7674-9056","position":8,"is_corresponding":false},{"id":1255573,"name":"Austin T. Gregg","orcid":"0009-0006-5741-9840","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T02:07:02.142014Z","pmid":"38922557","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}