Proteomic insights into inflammatory and angiogenic pathways distinguishing uveitic and neovascular glaucoma

Uveitic glaucoma and neovascular glaucoma (NVG) exhibit distinct clinical characteristics, yet the specific molecular alterations in the aqueous humor (AH) associated with each subtype remain poorly understood. In this study, we performed a proteomic analysis of AH samples from patients with uveitic glaucoma (n = 7), NVG (n = 5), and age-matched cataract patients (controls, n = 8) to identify potential biomarkers and elucidate subtype-specific molecular pathways. We applied advanced statistical approaches, including partial least squares discriminant analysis, multivariate receiver operating characteristic analysis, and least absolute shrinkage and selection operator regression, to identify key proteins involved in inflammation, fibrinolysis, and angiogenesis. Our results showed elevated levels of the complement components C1QC and C4A in both glaucoma subtypes, indicating a shared inflammatory profile, whereas pro-angiogenic factors such as SERPINF1 and HEXB were markedly upregulated in NVG, consistent with its neovascular phenotype. These findings underscore the distinct inflammatory and angiogenic signatures of uveitic glaucoma and NVG and provide novel insights into potential molecular targets for subtype-specific therapeutic strategies.