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Giovanni Luca Romano, Chiara B M Platania, Stefano Forte, Salvatore Salomone, Filippo Drago, Claudio Bucolo; Common miRNAs in Alzheimer’s disease and retinal degenerative diseases. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2275.
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© ARVO (1962-2015); The Authors (2016-present)
To identify common miRNAs in Alzheimer’s disease (AD), age related macular degeneration (AMD) and glaucoma. An important common characteristic to all these three diseases is the amyloid β deposition in the brain of AD patients and in the retina of AMD and glaucoma patients.
Human microRNA Disease Database (HMDD) and mir2Disease databases were used. No validated miRNAs are reported for glaucoma and AMD in HMDD and mir2Disease databses, thus a literature search has been carried out on PubMed and Scopus in order to identify miRNAs putatively involved in glaucoma and AMD. Hence, in order to increase the information available, we analyzed gene association studies on glaucoma and AMD, then the prediction of target miRNAs has been carried out by queries on microRNA.org database (http://www.microRNA.org/). Another enrichment analysis was performed by DIANA-miRPath v.2.0, calculating the probability for each miRNA to be significantly associated to a KEGG pathway.
Twenty, thirteen and nine deregulated miRNAs were found in AD, glaucoma and AMD respectively. In particular, we identified four miRNAs commonly deregulated in AD and AMD, and only one miRNA (miR29a) commonly deregulated in AD and glaucoma. We also identified five miRNAs commonly deregulated in glaucoma and AMD. Further, only one miRNA (miR21) was found deregulated matching all three neurodegenerative diseases. We enriched the information from literature predicting microRNA from target genes associated to AMD and glaucoma, and we found an increased number of common microRNA matching AD, AMD and glaucoma. We predicted the association of these eight common miRNA to KEGG pathways through TarBase annotation . The most representative KEGG pathways (higher number of miRNA and best p-values) are: “apoptosis” (hsa04210), “cytokine-cytokine receptor interaction” (hsa04060) and “Toll-like receptor signaling pathway” (hsa04620). Interesting the NF-kappa b signaling pathway is represented by one microRNA miR-146a-5p (p-value 2.6 e-10).
The implications of common miRNAs in the pathogenesis of AD and retinal degenerative diseases offer a novel approach to elucidate unclear molecular mechanisms of these conditions to explore novel therapeutic targets.
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