Altered MicroRNA Expression Profiles in Retinas with Diabetic Retinopathy

Abstract

Rats with streptozotocin (STZ)-induced diabetes were studied in order to identify abnormal microRNA (miRNA) expression profiles in diabetic retinopathy (DR) and to ascertain miRNAs associated with DR. Histopathologically, we observed characteristic features of DR in rats at 10 weeks after STZ injection. Investigation of miRNA expression profiles in the retinas of control and diabetic rats using miRNA microarrays revealed that many miRNAs were abnormally expressed in DR. On the basis of their fold changes and probability values, a total of 37 miRNAs were selected for further validation by real-time PCR analysis. The results showed that 11 miRNAs were significantly upregulated and 6 miRNAs were notably downregulated in DR. Furthermore, these changes in retinal miRNA expression levels paralleled the course of DR. Levels of miR-182, miR-96, miR-183, miR-211, miR-204, and miR-124 were significantly increased during the progress of DR, whereas miR-10b, miR-10a, miR-219-2-3p, miR-144, miR-338, and miR-199a-3p were significantly decreased. Our data indicate that the aberrant miRNA expression profiles in DR are associated with the development of DR. Modulation of retinal miRNA expression levels may provide a potential therapeutic strategy for DRs.

miR-23b-3p induces the cellular metabolic memory of high glucose in diabetic retinopathy through a SIRT1-dependent signalling pathway

“…In the present study, Produced as small, non-protein-coding RNAs, miRNAs are endogenous regulators that play significant roles in many cellular processes [33,34]. Accumulating evidence has recently illustrated the role of miRNAs in the pathogenesis of diabetes and its complications, including diabetic retinopathy [15,35,36]. The miRNA miR-125b plays a role in the dysregulation of Suv39h1 and associated chromatin H3K9me3 related to the increased expression of inflammatory genes in the vascular smooth muscle cells of diabetic mice.…”

“…MicroRNAs (miRNAs) represent an exciting area of research because of their involvement in many biological processes, including the development of metabolic diseases such as diabetes [15][16][17]. As highly conserved, short non-coding RNAs (21-25 nucleotides in length), miRNAs negatively regulate gene expression at the post-transcriptional level by binding to the 3′ untranslated region (3′-UTR) of target mRNA, leading to its degradation or translational repression [17].…”

microRNA-182 Mediates Sirt1-Induced Diabetic Corneal Nerve Regeneration

“…Further, we studied the role of miR-182 in TG sensory neurons because 1) miR-182 had the minimum P value; 2) miR-182 is a sensory organ-specific miRNA (19); and 3) miR-182 has been implicated in diabetic retinopathy (26), which occurs in parallel with nerve fiber alterations of the subbasal nerve plexus of diabetic corneas (27).…”

let-7 Contributes to Diabetic Retinopathy but Represses Pathological Ocular Angiogenesis

“…Several miRs, including let-7, miR-375, miR-9, miR-103/107, miR-143/145, and miR-144, have been shown to regulate insulin production, release, or insulin sensitivity (16)(17)(18)(19)(20)(21)(22). A number of miRs have been shown to be significantly regulated in the retinas or retinal ECs (RECs) in streptozotocin-induced or Akita (type I diabetic) DR animal models or in the oxygen-induced retinopathy model (23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Particularly, miR-146a and miR-146b are upregulated in the RECs of diabetic rats and act as negative feedback on NF-B activation to control the inflammatory response (23,33); miR-200b and miR-126 are downregulated in a DR mouse model and regulate VEGF expression during retinal neovascularization (25,29); miR-200b downregulation was also found in the retinas of patients with diabetes (25,34).…”