The potential role of m6A RNA methylation in diabetic retinopathy

Abstract

Diabetic retinopathy (DR), a major microvascular complication of diabetes, affects most diabetic individuals and has become the leading cause of vision loss. Metabolic memory associated with diabetes retains the risk of disease occurrence even after the termination of glycemic insult. Further, various limitations associated with its current diagnostic and treatment strategies like unavailability of early diagnostic and treatment methods, variation in treatment response from patient to patient, and cost-effectiveness have driven the need to find alternative solutions. Post-transcriptional epigenetic modification of RNA mainly, N6-methyladenosine (m6A), is an emerging concept in the scientific community. It has an indispensable effect in various physiological and pathological conditions. m6A mediates its effect through the various reader, writer, and eraser proteins. Recent studies have shown the impact of m6A RNA modification on various disease conditions, including diabetes, but its role in diabetic retinopathy is still unclear. However, change in m6A levels has been observed in various prime aggravators of DR pathogenesis, such as inflammation, oxidative stress, and angiogenesis. Further, various non-coding RNAs like microRNA, lncRNA, and circRNA are also associated with DR, and m6A has been shown to affect all these non-coding RNAs. This review is concerned with the possible mechanisms through which alteration in m6A modification of RNA can participate in the DR progression and pathogenesis and its expected role in metabolic memory phenomena.

Keywords: Diabetic retinopathy; Epitranscriptomics; Metabolic memory; m6A RNA methylation.