Role of Circulating Exosomal miRNA-3976 in Early Diabetic Retinopathy

Diabetic retinopathy (DR) remains as the most frequent complication of diabetes, and is the major cause of vision loss for middle-aged to elderly people. With longer life expectancies for people with diabetes, there is a significant rise in diabetic retinopathy worldwide. The treatment of DR is limited; and therefore, our study aimed to investigate the possibilities of circulating exosomal miRNAs in the early screening and prevention of DR; and to explore the function of the exosomal miRNAs in DR.

Eighteen participants were recruited and divided into two groups: the diabetes mellitus (DM) group and the DR group. We analyzed the expression profile of exosomal miRNAs derived from serum using RNA sequencing. Additionally, we conducted co-culture experiments of RGC-5 and HUVEC cells with DR-derived exosomes to examine the role of highly expressed exosomal miRNA-3976 in DR. Furthermore, we transfected RGC-5 and HUVEC cells with miRNA-3976 to investigate its effects.

Among the 1059 miRNAs analyzed, we identified eighteen up-regulated exosomal miRNAs. Treatment with DR-derived exosomes resulted in increased proliferation and reduced apoptosis of RGC-5 cells, and these effects were partially reversed by the miRNA-3976 inhibitor. Moreover, over-expression of miRNA-3976 led to increased apoptosis of RGC-5 cells and indirectly reduced the abundance of NFκB1.

Serum-derived exosomal miRNA-3976 has the potential to serve as a biomarker for DR, primarily exerting its effects in the early stages of DR through the regulation of NFκB-associated mechanisms.