Abstract
BACKGROUND: Patients with diabetes are at risk of developing diabetic keratopathy (DK). The pathophysiological mechanisms of DK and associated biomarkers remain unclear. However, tear analysis provides crucial insights into DK. Thus, we conducted a quantitative proteomic analysis of tears from DK patients to identify differentially expressed proteins and potential pathways associated with DK. METHODS: This prospective case-controlled study included patients admitted to Zhujiang Hospital between October 2022 and February 2023. We examined 22 eyes with DK and 11 control eyes without DK. General characteristics and dry eye-related features were recorded, including those observed using ocular surface analysis, conjunctival impression cytology, and tear ferning tests. Tear fluid was collected using Schirmer strips after ensuring group similarity in confounders. Proteins were analysed through four-dimensional label-free mass spectrometry. Differential proteins were subjected to analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction network map was constructed. RESULTS: Of the 2733 proteins identified, 313 (156 upregulated and 157 downregulated) differentially expressed proteins were screened. GO analysis revealed that these differentially expressed proteins mainly participated in mRNA decay, nuclear transcription, and receptor-mediated endocytosis. KEGG analysis showed that these differentially expressed proteins could be involved in pathways, such as arginine biosynthesis, extracellular matrix-receptor interactions. CONCLUSIONS: Arginine biosynthesis and extracellular matrix-receptor interactions may be involved in DK pathogenesis, and VDAC3 may be a potential biomarker for DK. These findings would enhance the understanding of DK among ophthalmologists as well as help in developing novel strategies for its treatment.