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David J Keegan, Hanan ElShelmani, Mike Wride; Identification of microRNA Biomarkers in AMD. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5250.
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© ARVO (1962-2015); The Authors (2016-present)
Can the circulating microRNAs (miRNA) profile identify those at risk of age-related macular degeneration (AMD)?This study investigated whether serum miRNAs have the potential to be used as biomarkers in identification of AMD and so may be used for rapid screening, early diagnosis, disease sub-typing, and/or treatment selection for AMD.The next objective of this study was to identify the functional roles differentially expressed miRNAs in AMD. It also demonstrates the miRNAs target genes and signalling pathways using computational tools for miRNAs prediction and identification.
This study initially involved total RNA isolation from sera specimens from patients with (i) atrophic AMD (n=10), (ii) neovascular AMD (n=10), and (iii) age- and gender-matched controls (n=10). 377 miRNAs were co-analysed in each of these specimens using array technologies and differentially regulated miRNAs were determined.More extensive validation studies (n=90) (i) atrophic AMD (n=30), (ii) neovascular AMD (n=30), and (iii) controls (n=30) were performed. 14 miRNAs were selected and co-analysed in each of these specimens using quantitative real-time polymerase chain reaction (qRT-PCR) in order to validate their expression.Finally, resulting differentially expressed miRNAs were investigated using bioinformatics approaches such as, DIANA-mirPath and miR TarBase. The target genes and signaling pathways data were incorporated with the differentially expressed miRNAs in AMD.
Unsupervised hierarchical clustering indicated that AMD serum specimens have a different miRNA profile compared to those of healthy controls. The study successfully identified and validated the differentially regulated miRNAs in serum from AMD patients versus controls. The biomarker potential of 3 miRNAs (miR-126, miR-19a and miR-410) was confirmed by qPCR, with significantly increased expression in serum of AMD patients compared to healthy controls.DIANA lab-mirPath database predicted a number of significant pathways that are regulated by these identified AMD circulating miRNA biomarkers, e.g. the complement and coagulation cascade.
Increased expression of microRNAs (miR-126, miR-410, and miR-19a) in AMD patients hold the potential to serve as diagnostic AMD biomarkers for both atrophic and neovascular AMD.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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