Abstract

The aim of our study is to evaluate the serum circulating levels of some miRNA, such as hsa-let-7b-5p, hsa-let-7a-5p, hsa-miR-320b, hsa-miR-23a-3p, hsa-miR-27a-3p, hsa-miR-15a-5p, and hsa-miR-495-3, in diabetic patients without diabetic retinopathy (DR), diabetic patients with DR, and, healthy subjects in order to find reliable and reproducible biomarkers for DR. A total of 45 subjects underwent serum sampling for miRNAs evaluation and a complete ophthalmologic examination, including microperimetry and widefield swept source optical coherence tomography angiography (OCTA). Total circulating RNA was isolated from patients using the miRNeasy Serum/Plasma Kit. Serum miRNA expression levels were significantly different in the three groups. In detail, circulating hsa-miR-15a-5p levels were significantly reduced in both diabetic patients without DR and diabetic patients with DR (p = 0.027). Serum hsa-miR-495-3p was lower in diabetic patients with DR and diabetic patients without DR (p = 0.049). Hsa-miR-23a-3p serum expression levels were significantly lower in diabetic patients with DR and diabetic patients without DR (p = 0.013). Significant associations of miRNAs with anatomical/perfusion parameters and functional parameters were observed in the diabetic groups. We find evidence of damage in progression biomarkers in DR that are evidently early in patients with diabetes without DR. Serum miRNAs levels are considered to have strong potential as a novel biomarker for the early detection of DR in subjects suffering from diabetes and could represent noninvasive target therapies to block the progression of the disease at the early stages.

Highlights

  • Diabetic retinopathy (DR) is the most frequent complication of diabetes mellitus (DM), characterized by microvascular changes in the retina [1]

  • A total of 45 subjects underwent serum sampling for miRNAs evaluation and a complete ophthalmologic examination, including microperimetry and widefield swept source optical coherence tomography angiography (OCTA)

  • Different studies have shown that some miRNAs are associated with glucose homeostasis, mostly in association with genes for diabetes-relevant pathways like insulin signaling [16,17,18]

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Summary

Introduction

Diabetic retinopathy (DR) is the most frequent complication of diabetes mellitus (DM), characterized by microvascular changes in the retina [1]. Due to the increased incidence of diabetes as a global epidemic disease, DR is estimated to occur for a third of people with diabetes, becoming the leading cause of preventable blindness in the working-age population in developed countries [2]. In the USA, it has been estimated that 40% of people with type 2 diabetes mellitus (T2DM) and 86% with type 1 diabetes (T1DM) will develop DR [3,4]. Diabetic retinopathy is divided into two major forms: nonproliferative (NPDR) and proliferative (PDR), named for the absence or presence of abnormal new blood vessels emanating from the retina. Additional information about the precise topographical distribution of such DR-related changes, like vessel density (VD), intercapillary spacing, or the vessel diameter index, could help the characterization of the disease [6]

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