Universität zu Köln

Grassmann, Felix ORCID: 0000-0003-1390-7528, Schoenberger, Peter G. A., Brandl, Caroline ORCID: 0000-0001-8223-6137, Schick, Tina, Hasler, Daniele ORCID: 0000-0002-1786-0563, Meister, Gunter, Fleckenstein, Monika ORCID: 0000-0001-8321-8037, Lindner, Moritz ORCID: 0000-0002-4416-3421, Helbig, Horst, 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). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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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:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Grassmann, Felix UNSPECIFIED orcid.org/0000-0003-1390-7528 UNSPECIFIED Schoenberger, Peter G. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brandl, Caroline UNSPECIFIED orcid.org/0000-0001-8223-6137 UNSPECIFIED Schick, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Hasler, Daniele UNSPECIFIED orcid.org/0000-0002-1786-0563 UNSPECIFIED Meister, Gunter UNSPECIFIED UNSPECIFIED UNSPECIFIED Fleckenstein, Monika UNSPECIFIED orcid.org/0000-0001-8321-8037 UNSPECIFIED Lindner, Moritz UNSPECIFIED orcid.org/0000-0002-4416-3421 UNSPECIFIED Helbig, Horst UNSPECIFIED UNSPECIFIED UNSPECIFIED Fauser, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Bernhard H. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-428879
DOI:	10.1371/journal.pone.0107461
Journal or Publication Title:	PLoS One
Volume:	9
Number:	9
Date:	2014
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PREVALENCE; SEVERITY; MICE; RNA Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42887