A Circulating MicroRNA Profile Is Associated with Late-Stage Neovascular Age-Related Macular Degeneration

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 d...

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Main Authors:	Grassmann, Felix, Schoenberger, Peter G. A., Brandl, Caroline, Schick, Tina, Hasler, Daniele, Meister, Gunter, Fleckenstein, Monika, Lindner, Moritz, Helbig, Horst, Fauser, Sascha, Weber, Bernhard H. F.
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159338/

id	pubmed-4159338
recordtype	oai_dc
spelling	pubmed-41593382014-09-12 A Circulating MicroRNA Profile Is Associated with Late-Stage Neovascular Age-Related Macular Degeneration Grassmann, Felix Schoenberger, Peter G. A. Brandl, Caroline Schick, Tina Hasler, Daniele Meister, Gunter Fleckenstein, Monika Lindner, Moritz Helbig, Horst Fauser, Sascha Weber, Bernhard H. F. Research Article 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, pcorrected = 5.610−5, hsa-mir-361-5p, pcorrected = 8.010−4 and hsa-mir-424-5p, pcorrected = 9.610−3). 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 = 1.210−8). 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 (pcorrected<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 TGFβ, 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. Public Library of Science 2014-09-09 /pmc/articles/PMC4159338/ /pubmed/25203061 http://dx.doi.org/10.1371/journal.pone.0107461 Text en © 2014 Grassmann et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Grassmann, Felix Schoenberger, Peter G. A. Brandl, Caroline Schick, Tina Hasler, Daniele Meister, Gunter Fleckenstein, Monika Lindner, Moritz Helbig, Horst Fauser, Sascha Weber, Bernhard H. F.
spellingShingle	Grassmann, Felix Schoenberger, Peter G. A. Brandl, Caroline Schick, Tina Hasler, Daniele Meister, Gunter Fleckenstein, Monika Lindner, Moritz Helbig, Horst Fauser, Sascha Weber, Bernhard H. F. A Circulating MicroRNA Profile Is Associated with Late-Stage Neovascular Age-Related Macular Degeneration
author_facet	Grassmann, Felix Schoenberger, Peter G. A. Brandl, Caroline Schick, Tina Hasler, Daniele Meister, Gunter Fleckenstein, Monika Lindner, Moritz Helbig, Horst Fauser, Sascha Weber, Bernhard H. F.
author_sort	Grassmann, Felix
title	A Circulating MicroRNA Profile Is Associated with Late-Stage Neovascular Age-Related Macular Degeneration
title_short	A Circulating MicroRNA Profile Is Associated with Late-Stage Neovascular Age-Related Macular Degeneration
title_full	A Circulating MicroRNA Profile Is Associated with Late-Stage Neovascular Age-Related Macular Degeneration
title_fullStr	A Circulating MicroRNA Profile Is Associated with Late-Stage Neovascular Age-Related Macular Degeneration
title_full_unstemmed	A Circulating MicroRNA Profile Is Associated with Late-Stage Neovascular Age-Related Macular Degeneration
title_sort	circulating microrna profile is associated with late-stage neovascular age-related macular degeneration
description	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, pcorrected = 5.610−5, hsa-mir-361-5p, pcorrected = 8.010−4 and hsa-mir-424-5p, pcorrected = 9.610−3). 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 = 1.210−8). 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 (pcorrected<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 TGFβ, 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.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159338/
_version_	1613132468782628864

A Circulating MicroRNA Profile Is Associated with Late-Stage Neovascular Age-Related Macular Degeneration

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