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Immune Checkpoint PD-L1 Modulates Retinal Microglial Activation to Alleviate Vascular Leakage in Choroidal Neovascularization via ERK

ABSTRACT: Neovascular age-related macular degeneration (NVAMD) is a common retinal disease causing vision loss in the elderly. Neuroinflammation significantly contributes to NVAMD's etiology. This study explores the role of PD-L1, an immune checkpoint in microglia, known for limiting neuroinflammation in neurodegenerative diseases, and its potential function in NVAMD. We found increased PD-L1 expression in retinal microglia following laser injury. PD-L1 knockout or inhibitory PD-L1 antibody treatment worsened vascular leakage and neoangiogenesis in a laser-induced NVAMD mouse model, effects reversible by microglia depletion with PLX5622. Blocking PD-L1 elevated pro-inflammatory factors and p-ERK levels, indicating microglial overactivation in NVAMD. Conversely, enhancing PD-L1 signaling reduced neuroinflammation and neovascularization via ERK. These findings highlight PD-L1's role in neoangiogenesis and neuroinflammation in NVAMD, suggesting its potential as a target for immunomodulatory treatment in NVAMD.

ORGANISM(S): Mus musculus

PROVIDER: GSE282544 | GEO | 2025/11/01

REPOSITORIES: GEO

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