Extracellular Vesicle-Derived miR-26b-5p is Up-Regulated in the Serum of Patients with Diabetic Retinopathy

Background: Diabetic retinopathy (DR) is a severe complication of diabetes; however, the pathogenesis of DR has not been completely clarified, which is mostly dependent on the molecular pathology. This study aimed to investigate key serum-derived miRNAs associated with DR. Methods: miRNA expression profile arrays of human umbilical vein endothelial cells (HUVECs) treated with glucose were downloaded from the Gene Expression Omnibus (GEO) database (GSE74296). Weighted gene co-expression network analysis (WGCNA) was performed to obtain hub miRNAs, which were verified in HUVECs treated with 40 mM and 5 mM glucose, respectively. Meanwhile, serum samples of patients with DR and healthy controls were collected, and EVs were extracted from the patients’ serum by ultracentrifugation. Hub miRNAs associated with endothelial dysfunction were verified in healthy individuals before and after treatment of patients with DR, by qRT-PCR. Results: These miRNAs were categorized into six modules, among which miR-26b-5p had a strong association with other modules. This miRNA was also one of the hyperglycemia-induced miRNAs related to endothelial dysfunction. miR-26b-5p was up-regulated in HUVECs treated with 40 mM glucose and in the serum of patients with DR before and after treatment. Furthermore, miR- 26b-5p was slightly up-regulated in serum-derived EVs but not in serum without EVs in DM patients. Conclusion: Our results suggest that EVs derived from miR-26b-5p are up-regulated in the serum of patients with DR.