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Neovascular AMD (nAMD) and proliferative diabetic retinopathy (PDR) are major blinding retinal diseases characterized by pathological angiogenesis. Using data-independent acquisition (DIA) proteomics, we analyzed aqueous humor from nAMD, PDR, and cataract control patients. Among 3186 identified proteins, 877 (nAMD) and 1017 (PDR) differentially expressed proteins (DEPs) were detected. Functional enrichment highlighted inflammatory and metabolic pathway dysregulation in both diseases. CDC42 and RHOA were consistently upregulated and implicated in cytoskeletal remodeling and angiogenesis. This study reveals shared molecular mechanisms in nAMD and PDR, proposing new targets for therapeutic intervention.