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Oxygen\u2010induced retinopathy (OIR) is a widely used ROP animal model. Icariin (ICA) has anti\u2010oxidative and anti\u2010inflammation properties; however, whether ICA has a regulatory effect on OIR remains unclear. In this study, ICA alleviated pathological neovascularization, microglial activation and blood\u2013retina barrier (BRB) damage in vivo. Further results indicated that endothelial cell tube formation, migration and proliferation were restored by ICA treatment in vitro. Proteomic microarrays and molecular mimicry revealed that ICA can directly bind to hexokinase 2 (HK2) and decrease HK2 protein expression in vivo and in vitro. In addition, ICA inhibited the AKT\/mTOR\/HIF1\u03b1 pathway activation. The effects of ICA on pathological neovascularization, microglial activation and BRB damage disappeared after HK2 overexpression in vivo. Similarly, the endothelial cell function was revised after HK2 overexpression. HK2 overexpression reversed ICA\u2010induced AKT\/mTOR\/HIF1\u03b1 pathway inhibition in vivo and in vitro. Therefore, ICA prevented pathological angiogenesis in OIR in an HK2\u2010dependent manner, implicating ICA as a potential therapeutic agent for ROP.<\/jats:p>","DOI":"10.1111\/imm.13818","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T10:23:20Z","timestamp":1716891800000},"page":"141-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Icariin alleviates oxygen\u2010induced retinopathy by targeting microglia hexokinase 2"],"prefix":"10.1111","volume":"173","author":[{"given":"Xingran","family":"Li","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Chongqing Medical 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