MicroRNA signatures in vitreous humour and plasma of patients with exudative AMD

Abstract

// Catherine Ménard 1 , Flavio A. Rezende 2 , Khalil Miloudi 4 , Ariel Wilson 3 , Nicolas Tétreault 1 , Pierre Hardy 5 , John Paul SanGiovanni 6 , Vincent De Guire 7 and Przemyslaw Sapieha 1,2,4 1 Department of Biochemistry, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada 2 Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada 3 Department of Engineering Physics, École Polytechnique de Montréal, Laser Processing and Plasmonics Laboratory, Montreal, Quebec, Canada 4 Departement of Neuroscience, McGill University, Montreal, Quebec, Canada 5 Departments of Pediatrics and Pharmacology, University of Montreal, Montreal, Quebec, Canada 6 Laboratory of Membrane Biochemistry and Biophysics, Nutritional Neuroscience Section, NIAAA, NIH, Bethesda, MD, United States of America 7 Department of Clinical Biochemistry, Maisonneuve-Rosemont Hospital, Quebec, Canada Correspondence to: Przemyslaw Sapieha, email: // Vincent De Guire, email: // Keywords : age-related macular degeneration, AMD, microRNAs, miRNA, biomarkers, Gerotarget Received : January 14, 2016 Accepted : March 10, 2016 Published : March 22, 2016 Abstract Age-related macular degeneration (AMD) is a leading cause of blindness worldwide affecting individuals over the age of 50. The neovascular form (NV AMD) is characterized by choroidal neovascularization (CNV) and responsible for the majority of central vision impairment. Using non-biased microRNA arrays and individual TaqMan qPCRs, we profiled miRNAs in the vitreous humour and plasma of patients with NV AMD. We identified a disease-associated increase in miR-146a and a decrease in miR-106b and miR-152 in the vitreous humour which was reproducible in plasma. Moreover, miR-146a/miR-106b ratios discriminated patients with NV AMD with an area under the Receiver Operating Characteristic curve (ROC AUC) of 0,977 in vitreous humour and 0,915 in plasma suggesting potential for a blood-based diagnostic. Furthermore, using the AMD Gene Consortium (AGC) we mapped a NV AMD-associated SNP (rs1063320) in a binding site for miR-152-3p in the HLA-G gene. The relationship between our detected miRNAs and NV AMD related genes was also investigated using gene sets derived from the Ingenuity Pathway Analysis (IPA). To our knowledge, our study is the first to correlate vitreal and plasma miRNA signatures with NV AMD, highlighting potential future worth as biomarkers and providing insight on NV AMD pathogenesis.