Unveiling purine metabolism targets in the pathogenesis of fungal Keratitis: A combined proteomics and metabolomics approach.

Fungal keratitis (FK) is a serious corneal infection that can cause severe eye pain, corneal perforation, and potentially lead to permanent vision loss or blindness. The study aims to identify potential therapeutic targets in the pathogenesis of FK using an integrated omics approach. FK model was established in C57BL/6 mice by infecting their corneas with Fusarium solani. Normal and infected corneas were analyzed using proteomics and untargeted metabolomics to identify co-enriched pathways. Differentially expressed metabolites (DEMs) in the key pathway were quantitatively analyzed with targeted metabolomics using mouse and human corneal samples. Integrated analysis revealed 84 upregulated and 50 downregulated co-enriched pathways (P < 0.05), with purine metabolism being the top pathway. Thirteen DEMs were enriched in purine metabolism, including downstream metabolites such as adenosine, adenosine monophosphate (AMP), inosine, hypoxanthine, xanthine, and uric acid. Targeted metabolomics showed decreased adenosine and AMP, and increased hypoxanthine, xanthine, and uric acid in infected corneas compared to normal corneas. Inosine showed higher level than the other metabolites in both groups. In human corneas, decreased adenosine and AMP, and increased uric acid were observed in infected corneas compared to normal corneas. Moreover, exogenous supplementation of adenosine and AMP in fungal culture systems effectively inhibited the growth of F. solani. The study highlights the role of purine metabolism in FK pathogenesis and unveils potential therapeutic targets for FK treatment.