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Identification of Novel Serum MicroRNAs in Age-Related Macular Degeneration
Hanan ElShelmani1, Michael A Wride1, Tahira Saad2
1Ocular Development and Neurobiology Research Group, Zoology Department, School of Natural Sciences, University of Dublin, Trinity College Dublin, Dublin, Ireland.
Purpose:
To identify circulating microRNAs (miRNA) associated with age-related macular degeneration (AMD). Thus differentially expressed serum miRNA could be used as AMD biomarkers.
Methods:
This study involved total RNA isolation from sera from patients with atrophic AMD (n = 10), neovascular AMD (n = 10), and age- and sex-matched controls (n = 10). A total of 377 miRNAs were coanalyzed using array technologies, and differentially regulated miRNAs were determined. Extensive validation studies (n = 90) of serum from AMD patients and controls confirmed initial results. Total RNA isolation was carried out from sera from patients with atrophic AMD (n = 30), neovascular AMD (n = 30), and controls (n = 30). Fourteen miRNAs from the discovery dataset were coanalyzed using quantitative real-time polymerase chain reaction (qRT-PCR) to validate their presence.
Results:
Unsupervised hierarchical clustering indicated that AMD serum specimens have a different miRNA profile to healthy controls. We successfully identified and validated the differentially regulated miRNAs in serum from AMD patients versus controls. The biomarker potential of three miRNAs (miR-126, miR-19a, and miR-410) was confirmed by qRT-PCR, with significantly increased quantities in serum of AMD patients compared with healthy controls.
Conclusions:
Increased quantities of miR-126, miR-410, and miR-19a in serum from AMD patients indicate that these miRNAs could potentially serve as diagnostic AMD biomarkers. All three miRNAs significantly correlated with AMD pathogenesis.
Translational Relevance:
The discovery of new AMD miRNA may act as biomarkers in evaluating AMD diagnosis and prognosis.
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