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By integrating single\u2010cell transcriptomic profiling of human fibrovascular membranes with murine disease models, we identified a TSPAN4\u2010associated microglial state characterized by a pro\u2010angiogenic and activated transcriptional program. Spatially, TSPAN4\u2010expressing microglia accumulated around pathological vascular tufts, and suppression of TSPAN4 attenuated RNV in the oxygen\u2010induced retinopathy (OIR) model. Under high\u2010glucose and hypoxic conditions, microglia upregulated TSPAN4 expression and triggered the biogenesis of migrasomes along retraction fibers. Microglia\u2010derived migrasomes were sufficient to promote endothelial angiogenic responses in vitro and pathological neovascularization in vivo. Mechanistically, transcriptomic analyses revealed that microglial migrasomes exerted pro\u2010angiogenic effects by activating the HIF\u20101\u03b1\/VEGF pathway in endothelial cells. In parallel, migrasomes reinforced a pro\u2010inflammatory microglial phenotype, establishing a pathogenic feed\u2010forward loop that amplified retinal vascular injury. Collectively, our findings define TSPAN4\u2010dependent migrasome formation as a critical mechanism through which microglia promote pathological RNV and uncover migrasome\u2010mediated communication as a previously unrecognized mode of immune\u2010vascular crosstalk. Targeting the microglial TSPAN4\u2010migrasome axis represents a promising therapeutic strategy for neovascular retinal diseases.<\/jats:p>","DOI":"10.1002\/advs.77711","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T06:49:23Z","timestamp":1789368563000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microglial TSPAN4\u2010Dependent Migrasomes Promote Pathological Retinal Neovascularization via Immune\u2010Vascular Crosstalk"],"prefix":"10.1002","author":[{"given":"Jingyi","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Nanjing Medical University  Nanjing 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