MicroRNA Expression in the Aqueous Humor of Patients with Diabetic Macular Edema

Abstract

We identified and compared secreted microRNA (miRNA) expression in aqueous humor (AH) and plasma samples among patients with: type 2 diabetes mellitus (T2D) complicated by non-proliferative diabetic retinopathy (DR) associated with diabetic macular edema (DME) (DME group: 12 patients); T2D patients without DR (D group: 8 patients); and non-diabetic patients (CTR group: 10 patients). Individual patient AH samples from five subjects in each group were profiled on TaqMan Low Density MicroRNA Array Cards. Differentially expressed miRNAs identified from profiling were then validated in single assay for all subjects. The miRNAs validated in AH were then evaluated in single assay in plasma. Gene Ontology (GO) analysis was conducted. From AH profiling, 119 mature miRNAs were detected: 86 in the DME group, 113 in the D group and 107 in the CTR group. miRNA underexpression in the DME group was confirmed in single assay for let-7c-5p, miR-200b-3p, miR-199a-3p and miR-365-3p. Of these four, miR-199a-3p and miR-365-3p were downregulated also in the plasma of the DME group. GO highlighted 54 validated target genes of miR-199a-3p, miR-200b-3p and miR-365-3p potentially implied in DME pathogenesis. Although more studies are needed, miR-200b-3p, let-7c-5p, miR-365-3p and miR-199a-3p represent interesting molecules in the study of DME pathogenesis.

Chronic and Transient Hyperglycemia Induces Changes in the Expression Patterns of IL6 and ADIPOQ Genes and Their Associated Epigenetic Modifications in Differentiating Human Visceral Adipocytes

“…A number of studies estimating plasma miRNAs in diabetic patients reported reduced levels of some of our studied miRNAs (miR-26a-5p, miR-365a-3p) [43,44]. On the other hand, we previously reported upregulated let-7d-5p, let-7e-5p, and miR-365a-3p in the VAT of female T2DM and impaired fasting glucose participants.…”

Protocol to analyze circulating small non-coding RNAs by high-throughput RNA sequencing from human plasma samples

“…To this aim, we suggest a data-driven approach based on the combination of three different algorithms as in Marabita et al. ( Marabita et al., 2016 ) and Grieco et al. 2020 ( Grieco et al., 2020 ) in order to establish candidate endogenous miRNAs to be exploited as reference normalizers.…”

“…( Marabita et al., 2016 ) and Grieco et al. 2020 ( Grieco et al., 2020 ) in order to establish candidate endogenous miRNAs to be exploited as reference normalizers. Each of the three algorithms generates a stability score such that a smaller score corresponds to higher expression stability combined into the summarized stability score (SSS) to select top candidate miRNAs in all three methods.…”

Non-Coding RNAs: Novel Players in Insulin Resistance and Related Diseases

“…Usually, extracellular miRNAs can be enclosed in extracellular vesicles, e.g., apoptotic bodies, microvesicles and exosomes, or associated with proteins—especially AGO2 [ 71 , 72 , 73 , 74 ]. Given their stability in several biological fluids, this class of small ncRNAs have been suggested as potential circulating biomarkers of different metabolic diseases, including diabetes [ 75 , 76 , 77 ].…”