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Conventional antivascular endothelial growth factor (anti\u2010VEGF) therapies indiscriminately suppress pathological and reparative angiogenesis and fail to correct the senescence\u2010 and inflammation\u2010driven microenvironment that sustains disease progression. Senescent endothelial cells (ECs) form the structural scaffold of pathological vessels, while neighboring senescent microglia exacerbate inflammatory signaling, together deteriorating the reactive oxygen species (ROS)\u2010rich vascular\u2010immune microenvironment. Here, we develop an injectable ROS\u2010responsive senolytic hydrogel (PCC1\/PHCF\u2010Gel) that enables lesion\u2010activated, sustained intraocular release of procyanidin C1 (PCC1), overcoming rapid clearance, oxidative degradation, and poor lesion retention associated with free PCC1. In oxygen\u2010induced retinopathy and choroidal neovascularization models, PCC1\/PHCF\u2010Gel markedly reduces retinal senescence, suppresses pathological neovascularization, and restores neuroretinal function, outperforming symptom\u2010directed therapies anti\u2010VEGF therapy. Single\u2010cell RNA sequencing reveals selective elimination of two pathogenic senescent cell subpopulations\u2014CXCR4\n                    <jats:sup>+<\/jats:sup>\n                    ECs and IFITM3\n                    <jats:sup>+<\/jats:sup>\n                    microglia\u2014thereby disrupting the reinforcing cycle of vascular and immune senescence and promoting reparative vascular regeneration. These findings establish a multifunctional, spatiotemporally controlled therapeutic paradigm and highlight PCC1\/PHCF\u2010Gel as a promising translational strategy for the precision treatment of OFN.\n                  <\/jats:p>","DOI":"10.1002\/advs.202523495","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:14:37Z","timestamp":1771272877000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dual\u2010Target ROS\u2010Driven Spatiotemporal Senolysis for Vascular Repair and Immune Microenvironment Reprogramming in the Treatment of Ocular Fundus Neovascularization"],"prefix":"10.1002","volume":"13","author":[{"given":"Yali","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Shanghai General Hospital Shanghai JiaoTong University School of Medicine National Clinical Research Center for Eye Diseases Shanghai Clinical Research Center for Eye 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Center for Precise Diagnosis and Treatment of Eye Diseases  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangjia","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Shanghai General Hospital Shanghai JiaoTong University School of Medicine National Clinical Research Center for Eye Diseases Shanghai Clinical Research Center for Eye Diseases Shanghai Key Clinical Specialty Shanghai Key Laboratory of Ocular Fundus Diseases Shanghai Engineering Center for Visual Science and Photomedicine Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Shanghai General Hospital Shanghai JiaoTong University School of Medicine National Clinical Research Center for Eye Diseases Shanghai Clinical Research Center for Eye Diseases Shanghai Key Clinical Specialty Shanghai Key Laboratory of Ocular Fundus Diseases Shanghai Engineering Center for Visual Science and Photomedicine Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Shanghai General Hospital Shanghai JiaoTong University School of Medicine National Clinical Research Center for Eye Diseases Shanghai Clinical Research Center for Eye Diseases Shanghai Key Clinical Specialty Shanghai Key Laboratory of Ocular Fundus Diseases Shanghai Engineering Center for Visual Science and Photomedicine Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Shanghai General Hospital Shanghai JiaoTong University School of Medicine National Clinical Research Center for Eye Diseases Shanghai Clinical Research Center for Eye Diseases Shanghai Key Clinical Specialty Shanghai Key Laboratory of Ocular Fundus Diseases Shanghai Engineering Center for Visual Science and Photomedicine Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Shanghai General Hospital Shanghai JiaoTong University School of Medicine National Clinical Research Center for Eye Diseases Shanghai Clinical Research Center for Eye Diseases Shanghai Key Clinical Specialty Shanghai Key Laboratory of Ocular Fundus Diseases Shanghai Engineering Center for Visual Science and Photomedicine Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases  Shanghai 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