Integrated proteomic profiling of aqueous humor reveals CDC42/RHOA-mediated pathogenic mechanisms in nAMD and PDR.

Neovascular age-related macular degeneration (nAMD) and proliferative diabetic retinopathy (PDR), though clinically distinct, are both sight-threatening ocular disorders driven by pathological neovascularization. However, their shared molecular mechanisms remain poorly characterized. In this study, we performed DIA quantitative proteomic analysis of aqueous humor (AH) from patients with nAMD, PDR, and control. A total of 3186 proteins were identified, in which 877 and 1017 differentially expressed proteins (DEPs) were detected in the nAMD and PDR groups, respectively, compared to control group. Functional enrichment analysis revealed significant involvement of inflammatory and metabolic pathways in both diseases. Notably, the persistent upregulation of cell division cycle 42 (CDC42) and ras homolog family member A (RHOA) in nAMD and PDR, combined with their established role in cytoskeletal remodeling, suggests their significant involvement in pathological angiogenesis. These findings offer novel perspectives on shared pathogenic pathways in neovascular ocular disorders and suggest potential therapeutic targets for further investigation.