Roles of noncoding RNAs in diabetic retinopathy: Mechanisms and therapeutic implications

Diabetic retinopathy (DR) is a microvascular complication of diabetes that leads to vision loss. The striking features of DR are hard exudate, cotton-wool spots, hemorrhage, and neovascularization. The dysregulated retinal cells, encompassing microvascular endothelial cells, pericytes, Müller cells, and adjacent retinal pigment epithelial cells, are involved in the pathological processes of DR. According to recent research, oxidative stress, inflammation, ferroptosis, pyroptosis, apoptosis, and angiogenesis contribute to DR. Recent advancements have highlighted that noncoding RNAs could regulate diverse targets in pathological processes that contribute to DR. Noncoding RNAs, including long noncoding RNAs, microRNAs (miRNA), and circular RNAs, are dysregulated in DR, and interact with miRNA, mRNA, or proteins to control the pathological processes of DR. Hence, modulation of noncoding RNAs may have therapeutic effects on DR. Small extracellular vesicles may be valuable tools for transferring noncoding RNAs and regulating the genes involved in progression of DR. However, the roles of noncoding RNA in developing DR are not fully understood; it is critical to summarize the mechanisms for noncoding RNA regulation of pathological processes and pathways related to DR. This review provides a fundamental understanding of the relationship between noncoding RNAs and DR, exploring the mechanism of how noncoding RNA modulates different signaling pathways, and pave the way for finding potential therapeutic strategies for DR.