International Journal of Nanomedicine (Jul 2023)
Role of Circulating Exosomal miRNA-3976 in Early Diabetic Retinopathy
Abstract
Songtao Yang,1,2 Jiaoyue Zhang,1,2 Tianshu Zeng,1,2 Juan Zheng,1,2 Jie Min,1,2 Lulu Chen1,2 1Department of Endocrinology, Union Hospital, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, People’s Republic of China; 2Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Lulu Chen, Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email [email protected]: 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.Materials and Methods: 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.Results: 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.Conclusion: 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.Keywords: exosomes, miRNAs, diabetes, diabetic retinopathy
