Noncoding RNAs Are Promising Therapeutic Targets for Diabetic Retinopathy: An Updated Review (2017–2022)

Abstract

Diabetic retinopathy (DR) is the most common complication of diabetes. It is also the main cause of blindness caused by multicellular damage involving retinal endothelial cells, ganglial cells, and pigment epithelial cells in adults worldwide. Currently available drugs for DR do not meet the clinical needs; thus, new therapeutic targets are warranted. Noncoding RNAs (ncRNAs), a new type of biomarkers, have attracted increased attention in recent years owing to their crucial role in the occurrence and development of DR. NcRNAs mainly include microRNAs, long noncoding RNAs, and circular RNAs, all of which regulate gene and protein expression, as well as multiple biological processes in DR. NcRNAs, can regulate the damage caused by various retinal cells; abnormal changes in the aqueous humor, exosomes, blood, tears, and the formation of new blood vessels. This study reviews the different sources of the three ncRNAs—microRNAs, long noncoding RNAs, and circular RNAs—involved in the pathogenesis of DR and the related drug development progress. Overall, this review improves our understanding of the role of ncRNAs in various retinal cells and offers therapeutic directions and targets for DR treatment.

Classical and Innovative Evidence for Therapeutic Strategies in Retinal Dysfunctions

“…As we have briefly mentioned, when talking about ncRNAs associated with retinopathy development, it is possible to modulate the levels of some of these molecules to yield a beneficial effect in DR. This can be achieved by either using antagonist molecules to inhibit pro-DR endogenous miRNAs or miRNA mimics to rescue the anti-DR pathways [108,158].…”

Relationship between Biochemical Pathways and Non-Coding RNAs Involved in the Progression of Diabetic Retinopathy

“…Researchers mainly use endothelial cells, glial, or RPE cells as biological material. Visual cells, bipolar cells, horizontal cells, amacrine cells, and reticular cells are more difficult to obtain the research material for [ 142 ]. Moreover, it is not easy to apply the ncRNAs detected in experimental studies to clinical practice.…”

“…In the future, research on this new class of biomarkers may be included in the early and precise diagnosis of diabetes and its complications, including DR, and will also help select the appropriate therapy for a specific patient. However, further research on the practical use of ncRNAs will enable clinicians to diagnose DR earlier and make the treatment effective [ 142 ].…”

“…The correlation of ncRNA profiles with DR indicates their involvement in molecular pathways, which are important in the pathomechanism of diabetic retinopathy. ncRNAs are involved in the regulation of retinal cell damage, vascular changes in choroidal vessels, inflammation in RPE cells, leukostasis, neovascularization, neurodegeneration, and antioxidant defense capacity [ 142 ]. Therefore, ncRNA profiling in body fluids has increasingly promising applications in the prognosis, monitoring, and diagnosis of DR. Clinically useful molecular diagnostic tests are one of the most important applications of ncRNA profiling.…”

Exosomal noncoding RNA: A potential therapy for retinal vascular diseases

“… 56 , 57 , 58 , 59 , 60 Many studies investigated ncRNAs for their roles in retinal vascular diseases, including retinal vascular formation, inflammation, and cell death. 61 , 62 , 63 , 64 , 65 , 66 miRNAs, one of the small ncRNAs, have been the most extensively studied among ncRNAs in the development and progression of retinal vascular diseases. 63 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 In particular, miR-204-5p inhibits SMAD family member 2/3 ( SMAD2/3 ) mRNA in DR, suppressing vascular endothelial cell proliferation.…”