Serum MiRNA Biomarkers serve as a Fingerprint for Proliferative Diabetic Retinopathy

Abstract

Background: Diabetic retinopathy (DR) is a retinopathy resulting from diabetes mellitus (DM) which was classified into non-proliferative DR (NPDR) and proliferative DR (PDR). Without an early screening and effective diagnosis, patients with PDR will develop serious complications. Therefore, we sought to identify special serum microRNAs (miRNAs) that can serve as a novel non-invasive screening signature of PDR and test its specificity and sensitivity in the early diagnosis of PDR. Methods: In total, we obtained serum samples from 90 PDR cases, 90 matched NPDR patients and 20 controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA). The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR (RT-qPCR) arranged in an initial and a two-stage validation sets. Moreover, additional double-blind testing was performed in 20 patients clinically suspected of having DR to evaluate the diagnostic value and accuracy of the serum miRNA profiling system in predicting PDR. Results: Three miRNAs were significantly increased in patients with PDR compared with NPDR after the multiple stages. The areas under the receiver operating characteristic (ROC) curves of the validated three-serum miRNAs signature were 0.830, 0.803 and 0.873 in the initial and two validation sets, respectively. Combination of miR-21, miR-181c, and miR-1179 possessed a moderate ability to discrimination between PDR and NPDR with an area under ROC value of 0.89. The accuracy rate of the three-miRNA profile as PDR signature was 82.6%. Conclusions: These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of PDR. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of PDR from NPDR.

Oxidative Stress Biomarkers for Diabetic Retinopathy and Medical Management Affecting Oxidative Stress

“…Various recent reports have demonstrated alterations in miRNA expression in diabetic eyes. Subjects with proliferative and nonproliferative DR have different serum levels of miR-21, miR-181c, and miR-1179 [96]. Downregulation of miR-200b was observed in the retina in diabetes.…”

Biomarkers in Diabetic Retinopathy

“…Clinical tests, biochemical markers, and molecular factors, with the latter including genetic and epigenetic markers [4]. 2.…”

“…Recently, three miRNAs in serum of patients with diabetic retinopathy have been reported as potential biomarkers of the disease [4,302,306]. Our team is currently taking a discovery rather than a candidate approach to microRNAs for latestage diabetic retinopathy, and recently published a paper highlighting the impact of the instrumentation used for detection of these molecular biomarkers [85].…”

Circulating microRNAs and diabetes: potential applications in medical practice

“…Thus, new biomarkers would be useful to improve the detection of these complications. Interestingly, a study revealed three serum miRNAs (miR-21, -181c, -1179) that are deregulated in patients with proliferative diabetic retinopathy vs those with non-proliferative retinopathy suggesting that circulating miRs could be non-invasive biomarkers for the detection and/or the follow-up of retinopathy [66]. Furthermore, in a small cohort, a higher level of several miRNAs related to angiogenesis (miR-15a, -320a, -320b, -93, -29a) was found in vitreous humour of patients with proliferative diabetic retinopathy compared with patients with macular hole, with some of these miRNAs also deregulated in the serum [67].…”