Grassmann, Felix and Schoenberger, Peter G. A. and Brandl, Caroline and Schick, Tina and Hasler, Daniele and Meister, Gunter and Fleckenstein, Monika and Lindner, Moritz and Helbig, Horst and Fauser, Sascha and Weber, Bernhard H. F. (2014) A Circulating MicroRNA Profile Is Associated with Late-Stage Neovascular Age-Related Macular Degeneration. PLOS ONE, 9 (9): e107461. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Age-related macular degeneration (AMD) is the leading cause of severe vision impairment in Western populations over 55 years. A growing number of gene variants have been identified which are strongly associated with an altered risk to develop AMD. Nevertheless, gene-based biomarkers which could be dysregulated at defined stages of AMD may point toward key processes in disease mechanism and thus may support efforts to design novel treatment regimens for this blinding disorder. Circulating microRNAs (cmiRNAs) which are carried by nanosized exosomes or microvesicles in blood plasma or serum, have been recognized as valuable indicators for various age-related diseases. We therefore aimed to elucidate the role of cmiRNAs in AMD by genome-wide miRNA expression profiling and replication analyses in 147 controls and 129 neovascular AMD patients. We identified three microRNAs differentially secreted in neovascular (NV) AMD (hsa-mir-301-3p, p(corrected) = 5.6*10(-5), hsa-mir-361-5p, p(corrected) = 8.0*10(-4) and hsa-mir-424-5p, p(corrected) = 9.6*10(-3)). A combined profile of the three miRNAs revealed an area under the curve (AUC) value of 0.727 and was highly associated with NV AMD (p = 1.2*10(-8)). To evaluate subtype-specificity, an additional 59 AMD cases with pure unilateral or bilateral geographic atrophy (GA) were analyzed for microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p. While we found no significant differences between GA AMD and controls neither individually nor for a combined microRNAs profile, hsa-mir-424-5p levels remained significantly higher in GA AMD when compared to NV (p(corrected)<0.005). Pathway enrichment analysis on genes predicted to be regulated by microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p, suggests canonical TGF beta, mTOR and related pathways to be involved in NV AMD. In addition, knockdown of hsa-mir-361-5p resulted in increased neovascularization in an in vitro angiogenesis assay.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PREVALENCE; SEVERITY; MICE; RNA; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde Medicine > Lehrstuhl für Humangenetik Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Aug 2019 09:14 |
| Last Modified: | 14 Aug 2019 09:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9561 |
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