Preliminary proteome characterization of the aqueous humor across four cataract subtypes

This study aimed to characterize proteomic alterations in the aqueous humor (AH) across cataract subtypes and to identify subtype-specific pathological signatures for molecular stratification. Four-dimensional data-independent acquisition mass spectrometry was performed for comprehensive proteomic profiling of AH samples from 40 cataract patients in this pilot study. Functional annotation using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses elucidated biological pathways. Univariate and multivariate statistical analyses were applied to identify Differentially Abundant Proteins (DAPs), and orthogonal partial least squares discriminant analysis (O-PLS-DA) was used to screen candidate discriminatory signatures. A total of 1905 proteins were identified, predominantly enriched in pathways related to inflammatory and immune responses, cell adhesion, extracellular matrix organization, and energy metabolism. Compared with age-related cataract, 96, 119, and 272 candidate DAPs were identified in diabetic cataract, high myopic cataract, and cataract with anterior capsule fibrosis, respectively, among which 24 proteins were identified as shared signatures across these subtypes. By integrating top-ranked DAPs with high-VIP molecules from the O-PLS-DA model, we identified 32 candidate proteins for discriminating between cataract subtypes. These findings delineate subtype-associated candidate proteomic signatures in AH, providing valuable insights that facilitate mechanistic stratification and support the identification of subtype-specific therapeutic targets.