Integrated proteomic and metabolomic profiling reveals molecular signatures in cataract patients

Objective: This study aimed to characterize systemic molecular signatures in the serum of patients with age-related cataracts and explore specific variations through integrated proteomic and metabolomic profiling. Methods: Serum samples from 17 cataract patients and 24 healthy controls were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic and metabolomic profiling. Differentially expressed proteins (DEPs) and metabolites (DEMs) were identified using multivariate statistics. Functional enrichment and multi-omics integration analyses were performed to identify key biological pathways. Key proteins were validated via enzyme-linked immunosorbent assay (ELISA) in an independent cohort (n=136). Results: We identified 257 DEPs and 51 significant DEMs in cataract patients. Downregulated proteins included peroxiredoxin 6 (PRDX6), biliverdin reductase B (BLVRB), glycolytic enzyme phosphoglycerate kinase 1 (PGK1), and chaperone peptidylprolyl isomerase A (PPIA), while oxidative stress-related metabolites were elevated. Age-stratified analysis showed distinct profiles in younger patients (45-55 years). Multi-omics integration demonstrated strong correlation between proteome and metabolome, with co-enrichment in pathways such as prolactin signaling and diabetic cardiomyopathy. ELISA validation confirmed decreased levels of PGK1 and PPIA in an independent cohort. Conclusions: Our findings reveal systemic molecular alterations in age-related cataracts, highlighting oxidative stress and metabolic dysregulation with age-specific patterns. These results provide insights into cataract pathogenesis and potential biomarkers for personalized risk assessment.