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Neuroinflammation significantly contributes to NVAMD's etiology. This study explores the role of Programmed cell death ligand 1 (PD\u2010L1), an immune checkpoint (ICP) in microglia, known for limiting neuroinflammation in neurodegenerative diseases, and its potential function in NVAMD. This work finds increased PD\u2010L1 expression in retinal microglia following laser injury. PD\u2010L1 knockout (KO) or inhibitory PD\u2010L1 antibody treatment worsens vascular leakage and neoangiogenesis in a laser\u2010induced NVAMD mouse model, effects reversible by microglia depletion with PLX5622. This study underscores that choroidal neovascularization (CNV) may be regulated by multiple mechanisms, with PD\u2010L1 modulation representing one of these pathways. Blocking PD\u2010L1 elevated proinflammatory factors and p\u2010ERK levels, indicating microglial overactivation in NVAMD. Conversely, enhancing PD\u2010L1 signaling reduced neuroinflammation and neovascularization via ERK. These findings highlight PD\u2010L1's role in neoangiogenesis and neuroinflammation in NVAMD, suggesting its potential as a target for immunomodulatory treatment in NVAMD.<\/jats:p>","DOI":"10.1002\/advs.202400747","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T04:10:04Z","timestamp":1747800604000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Immune Checkpoint PD\u2010L1 Modulates Retinal Microglial Activation to Alleviate Vascular Leakage in Choroidal Neovascularization via ERK"],"prefix":"10.1002","volume":"12","author":[{"given":"Yue","family":"Zou","sequence":"first","affiliation":[{"name":"Eye Institute and Department of Ophthalmology Eye &amp; ENT Hospital NHC Key Laboratory of Myopia (Fudan University); Key Laboratory of Myopia Chinese Academy of Medical Sciences Shanghai Key Laboratory of Visual Impairment and Restoration Fudan University Shanghai 200031 China"},{"name":"The State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science and the Institutes of Brain Science Fudan University Shanghai 200032 China"},{"name":"Department of Ophthalmology Yunnan Eye Institute &amp; 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