Proteomic analysis of corneal epithelial cells in patients with neurotrophic keratopathy.

PURPOSE: This study aimed to identify proteomic differences in the corneal epithelium of Neurotrophic Keratopathy (NK) patients with or without HSV-1 infection compared to normal donors.

METHODS

Samples were divided into HSV-1-infected and non-infected NK groups, plus a control group. Corneal epithelial specimens were obtained via curettage/debridement, treated with TMT reagent, and analyzed by HPLC-MS/MS. Differentially expressed proteins underwent GO, KEGG, GSEA, and protein-protein interaction network analyses, with Western blotting validation.

RESULTS

Compared to controls, non-HSV-1 NK patients showed 1228 differentially expressed proteins (771 downregulated, 457 upregulated), while HSV-1-infected NK patients had 939 (617 downregulated, 322 upregulated). Differential proteins play significant roles in many biological processes and pathways, such as epithelial-mesenchymal transition and interferon gamma response. Compared with the control group, there were 569 common differentially expressed proteins in HSV-1 infection and non-infection. We selected the top three upregulated proteins and the downregulated proteins. Their Western blotting results were consistent with the proteomics results.

CONCLUSION

This study has laid the foundation for the research on the mechanism of NK. It has been discovered that the upregulated (S100A2, TGM1, RPS28) and downregulated (ADH1C, EZH1, CHP2) proteins, which are significantly downregulated in the corneal epithelium of NK patients, may be used as diagnostic markers or therapeutic targets for NK in clinical practice.