Abstract
Purpose:
Age-related macular degeneration (AMD) is the leading cause of blindness affecting people over the age of 50. The exudative form, known as neovascular AMD (NV AMD) and is characterized by choroidalneo-vascularization (CNV). Recently, a number of studies have demonstrated specific micro-RNA (miRNA) signatures in plasma or urine for several diseases such as cancers and kidney disease. MiRNAs are small non-coding RNA of 22-24 nucleotides length which can circulate in human body fluids. To date, there is a lack of information on miRNA signatures associated with NV AMD. The aim of this study is to detect miRNA profiles in the vitreous and plasma of patients with NV AMD.
Methods:
All patients were previously diagnosed with AMD (with CNV) and were followed and operated by a single vitreoretinal surgeon (F.A. Rezende) before receiving anti-VEGF treatment (AVASTIN). Control patients underwent surgical treatment for nonvascular pathology (epiretinal membrane or macular hole). In addition, for plasma miRNA detection, blood was collected the same day prior to the surgery. First, a screening of miRNAs in vitreous samples (3 controls and 4 AMD) was performed by microarray (including 384 miRNAs). Next, we validated miRNA profiles in both vitreous and plasma with individual TaqMan qPCRs with a higher number of patients (n=15) in each group.
Results:
Microarray analysis identified significantly higher levels of miR-548a (2-fold) and miR-146a (4-fold) and lower levels of miR-16, miR-152 and miR-106b in human vitreous from patients with NV AMD when compared to controls. Individual qPCRs validated vitreous expression patterns of miR-146a, miR-106b and miR-152. In addition, analysis of plasma miRNAs by TaqMan miRNA assay identified a decrease in the level of miR-152 and miR-106b. In contrast, plasma levels of miR-146a were not significantly induced in the AMD group as they were for vitreous samples. Importantly, no correlation was drawn for miRNA profiles and patient age.
Conclusions:
To our knowledge, our study is the first to characterize miRNA profiles in both vitreous and plasma from a cohort of patients suffering from NV AMD. Identification of a miRNA signature in circulation is conceptually promising for future development of a novel class of biomarkers for NV AMD. Moreover, elucidating miRNA profiles may provide insight on gene regulation during disease progression and potentially provide novel therapeutic avenues.