Olink proteomics profiling reveals metabolism-related protein biomarkers in diabetic retinopathy

Diabetic retinopathy (DR) represents a microvascular complication of diabetes mellitus that is associated with metabolic dysregulation. This study employed Olink proteomics profiling to identify novel biomarkers and elucidate the potential mechanism of DR. A total of 44 patients with DR and 44 individuals with cataracts serving as controls were enrolled in the study. Aqueous humor samples from all participants were analyzed for 92 metabolism-related proteins using the Olink® Metabolism Panel. Differential expression analysis identified 78 proteins with altered expression between the two groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed proteins revealed that the enriched pathways were primarily associated with blood vessel development, cellular signaling, and protein degradation. Notably, TFF2 exhibited exceptional diagnostic potential for DR with an area under the curve (AUC) of 0.9974 in receiver operating characteristic (ROC) analysis. Elevated TFF2 levels were further validated in both DR patients and a streptozotocin (STZ)-induced diabetic murine model. Functional experiments revealed that TFF2 contributed to endothelial angiogenic effects in vitro and retinal vascular dysfunction in vivo. These findings underscore the potential of TFF2 as a diagnostic biomarker for DR and offer new insights into the metabolic pathways driving DR pathogenesis.