First Global Assessment of Circulating microRNAs as Diagnostic and Prognostic Biomarkers for Diabetic Retinopathy

Abstract

Purpose: To explore the role of circulating miRNAs as biomarkers and pathogenic determinants of disease progression and early detection of diabetic complications of the retina.

Methods: We have profiled circulating miRNAs in patients with DR. Total RNA was extracted from whole blood from 99 subjects (20 healthy control, Gr1; 40 diabetes without any complication, Gr2; 20 diabetes with non-proliferative DR, Gr3; and 19 diabetes with proliferative DR, Gr4). 35 candidate miRNAs were identified through microarray screening among Gr1 (pool 5 individual RNA samples) and Gr2 (pool 5 individual RNA samples) to be markers for diabetes.

Results: Upon validation, we found that the expression levels of miR-126, miR-128 and miR-15a were significantly modulated as the DR developed and progressed. We used miR-451a (red blood cell marker) as our normalization control because with type 2 diabetes there is no change of red blood cell number. This data set is a product of a robust multivariable biostatistical analysis. Ingenuity pathway analysis suggested the miRNAs may impair angiogenic signaling, especially VEGF-dependent pathway, in patients with type 2 diabetes.

Conclusions: The results suggest that circulating miRNAs, in particular miR-126, miR-128 and miR-15a, may play an important role in the pathogenesis of DR. miRNAs may be potential candidates for Next Generation biomarkers.

Keywords: 499 diabetic retinopathy • 688 retina