MicroRNA and diabetic retinopathy—biomarkers and novel therapeutics

Abstract

Diabetic retinopathy (DR) accounts for ~80% of legal blindness in persons aged 20-74 years and is associated with enormous social and health burdens. Current therapies are invasive, non-curative, and in-effective in 15-25% of DR patients. This review outlines the potential utility of microRNAs (miRNAs) as biomarkers and potential therapy for diabetic retinopathy. miRNAs are small noncoding forms of RNA that may play a role in the pathogenesis of DR by altering the level of expression of genes via single nucleotide polymorphism and regulatory loops. A majority of miRNAs are intracellular and specific intracellular microRNAs have been associated with cellular changes associated with DR. Some microRNAs are extracellular and called circulatory microRNAs. Circulatory miRNAs have been found to be differentially expressed in serum and bodily fluid in patients with diabetes mellitus (DM) with and without retinopathy. Some miRNAs have been associated with the severity of DR, and future studies may reveal whether circulatory miRNAs could serve as novel reliable biomarkers to detect or predict retinopathy progression.Therapeutic strategies can be developed utilizing the natural miRNA/long noncoding RNA (lncRNA) regulatory loops. miRNAs and lncRNAs are two major families of the non-protein-coding transcripts.They are regulatory molecules for fundamental cellular processes via a variety of mechanisms, and their expression and function are tightly regulated. The recent evidence indicates a cross-talk between miRNAs and lncRNAs. Therefore, dysregulation of miRNAs and lncRNAs is critical to human disease pathogenesis, such as diabetic retinopathy. miRNAs are long-distance communicators and reprogramming agents, and they embody an entirely novel paradigm in cellular and tissue signaling and interaction. By targeting specific miRNAs, whole pathways implicated in the pathogenesis of DR may potentially be altered. Understanding the endogenous roles of miRNAs in the pathogenesis of diabetic retinopathy could lead to novel diagnostic and therapeutic approaches to managing this frequently blinding retinal condition.

Developmental Regulation and Functional Prediction of microRNAs in an Expanded Fasciola hepatica miRNome

“…For example, miRNA mimics or inhibitors could be used to manipulate transcript expression alongside or in place of RNA interference (RNAi) methods. These new approaches could be useful for laboratory-based functional genomics, or even as new avenues for control [miRNAs have been suggested as therapeutic targets in various human diseases ( Marracino et al., 2021 ; Shi et al., 2021 ; Smit-McBride and Morse, 2021 )]. Furthermore, inhibiting EV release from helminths would conceivably prevent delivery of miRNAs (and other bioactive molecules) to host immune cells.…”

The Protective Effects of Neurotrophins and MicroRNA in Diabetic Retinopathy, Nephropathy and Heart Failure via Regulating Endothelial Function

“…miRNAs are highly conserved, endogenous, small, non-coding RNAs with a length of ~22 nucleotides, that regulate gene expression by binding to partially complementary sequences of mRNA [ 132 ]. In cardiac insufficiency, chronic immune activation and aberrant miRNA expression are consistently evident [ 133 , 134 ].…”

“…New approaches to treat DR are being developed via precision medicine that aims to target novel epigenetic changes associated with the development of DR: amongst these approaches, targeting specific miRNA is a very promising avenue for managing DR [ 134 , 135 ]. The restoration of altered miRNA expression to normal levels has recently been shown as a promising approach to prevent diabetes-associated changes [ 2 , 7 , 20 ].…”

Early Neural Changes as Underlying Pathophysiological Mechanism in Diabetic Retinopathy

“…miRNA alterations have been observed in many disorders including DR. Most miRNA alterations in diabetes have been related to vascular changes, but some of them have also been related to inflammation [116]. A direct relationship between miRNAs and diabetic neural retinopathy has been established: miR29b and its potential target PKR associated protein X (RAX) are localized in retinal ganglion cells and cells of the inner nuclear layer and are upregulated in diabetes and, therefore, may be considered a therapeutic target [117].…”