Micro RNAs in the Aqueous Humor of Patients with Diabetic Macular Edema

Abstract

Purpose : MicroRNAs(miRNAs) have been studied as new biomarkers or mediators in various diseases, but the value of aqueous humor miRNAs in diabetic macular edema (DME) is still not known. We compared the expression of miRNAs and cytokines in patients with DME and healthy controls using the comparatively easy-to-access aqueous humor of intraocular specimens.

Methods : Prospective cross-sectional study. Twenty naïve DME patients and 13 control subjects, who were scheduled for intravitreal injection and cataract surgery respectively. Aqueous humor samples were collected at the beginning of each procedure and analyzed using a microarray composed of 84 miRNAs, RT-qPCR for verifying selected differentially expressed miRNAs, and a cytokine assay, the results of which were compared with bioinformatics conducted to find out genes associated with DME-related miRNAs.

Results : Five miRNAs(hsa-miR-185-5p, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-15b-5p, and hsa-miR-15a-5p) showing a fold change greater than -50 in log2 values in the microarray were selected, all significantly downregulated in the DME group compared to the control group (p<0.05), and showed a direct relationship with TNF, NFkB1, and IL-6 in bioinformatics analysis, all of which were related to VEGF. In the cytokine assay, the aqueous concentrations of VEGF, placental growth factor(PIGF), IL-6, and IL-8 were significantly higher in the DME group compared to the control group.

Conclusions : This study is the first to perform miRNA profiling of the aqueous humor of DME patients. This study may be meaningful because there is no established animal model for DME. All five statistically significantly differentially expressed miRNAs identified in our study are associated with angiogenesis and inflammation, both of which are closely related to DME pathogenesis. These miRNAs may be candidate novel therapeutic targets or biomarkers for DMO prognosis and drug response prediction.