Proteomic analysis of aqueous humor from patients with Fuchs endothelial corneal dystrophy reveals downregulated expression of HSP60

The aim of the study is to identify proteins with differential abundance among aqueous humor (AqH) samples from patients with mild or advanced Fuchs endothelial corneal dystrophy (FECD) compared to control subjects. Proteins were extracted from AqH samples and analyzed by liquid chromatography–mass spectrometry. A total of 455 proteins were identified across the three groups, of which 285 proteins were shared across all groups at the identification level and 104 were retained after proteomic filtering for quantitative analysis. Statistical analysis revealed that 48 proteins were significantly downregulated in mild, advanced, or both groups compared to controls, while one was upregulated. Functional enrichment analysis was performed on differentially expressed proteins (DEPs) and indicated that the main biological processes were associated with cell energy metabolism and cytoskeleton disorganization, known hallmarks of FECD pathology. Among all these, HSP60 was selected for further validation. Reduced HSP60 expression was confirmed in additional AqH samples and corneal endothelial tissue samples from FECD patients, supporting the proteomics findings. In conclusion, these results suggest that HSP60 is a disease-associated protein in FECD and a candidate for future functional studies, with possible relevance for biomarker discovery and therapeutic exploration.