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.