MicroRNA-200b Expression in the Vitreous Humor of Patients with Proliferative Diabetic Retinopathy

Abstract

Background: The role of microRNA (miRNA)-200b in the pathogenesis of proliferative diabetic retinopathy (PDR) has been studied in diabetic animal models. The aim of this study was to assess miRNA-200b expression in the vitreous of patients with PDR and to determine its correlation with vascular endothelial growth factor (VEGF), one of the pathogenic mechanisms in PDR. Methods: Quantitative reverse transcription polymerase chain reaction was used to measure miRNA-200b expression in the vitreous from 29 eyes with PDR and 30 eyes with idiopathic macular holes (IMH; control group). Vitreous VEGF was measured using an enzyme-linked immunosorbent assay. Results: miRNA-200bexpression was about 5-fold increased in the vitreous samples from eyes with PDR compared with the controls (p ≤ 0.001). Vitreous VEGF expression was also significantly higher in the PDR group than in the IMH group (p ≤ 0.001), but no significant correlation was found between miRNA-200b and VEGF. Conclusion: Both miRNA-200b and VEGF are increased in the vitreous of patients with PDR but in a noncorrelated pattern. miRNA-200b may be involved in the pathogenesis of PDR but through VEGF-independent mechanisms. Further studies are needed to identify the miRNA-200b-targeted genes involved in the pathogenesis of PDR and to examine the potential role of miRNA-200b as a target for PDR treatment.

Plasma levels of miR‐29b and miR‐200b in type 2 diabetic retinopathy

“…Despite the limitations, our findings support the perspective of using circulating miRNA levels as biomarkers of prognosis in type 2 diabetes and highlight the need for further research on them. As already recognized by other authors, although in vitro and animal studies are essential to elucidate the mechanistic effects, the same miRNAs may be differentially expressed between humans and animals, and even in different cell and tissue types, including vitreous, retinal endothelial cell and whole retina …”

“…Moreover, miR‐29b was not detected in the serum samples from the same patients . Plasma miR‐200b was up‐regulated in premature infants with retinopathy of prematurity stage 3 with plus disease, a proliferative vitreoretinopathy characterized by retinal ischaemia and neovascularization, while vitreous miR‐200b was increased in patients with PDR (41% type 2 diabetes) as compared to subjects with idiopathic macular holes …”

“…However, neither miR‐29b nor miR‐200b was investigated. Expression of either miR‐29b or miR‐200b was evaluated in studies in which patients with proliferative retinopathy were compared to non‐diabetic controls . Vitreous levels of miR‐29b did not differ between PDR patients (with diabetes type not reported) and subjects with macular hole, a non‐proliferative and non‐inflammatory disorder.…”

“…Given their high stability and omnipresence in body fluids, several studies have identified the potential of circulating miRNAs as biomarkers of diagnosis, prognosis and management of type 2 diabetes and its vascular complications . Despite this, the profile of circulating miRNAs in DR has been evaluated only recently …”

Landscape of microRNA in the aqueous humour of proliferative diabetic retinopathy as assessed by next‐generation sequencing

“…Due to their stability in biofluids such as blood, urine, and aqueous humour (AH), as well as their cell‐type and tissue specificity, miRNAs are potential biomarkers for the detection of DR . A few studies have detected miRNAs in the blood or vitreous humour of DR patients using microarray or polymerase chain reaction (PCR), and suggested that miRNA may be involved in DR and that some miRNAs may be biomarkers for DR . However, miRNA arrays or PCR have only been able to detect some of the mature miRNAs in the known miRbase database .…”