Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/45279
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dc.contributor.authorZhao, M-
dc.contributor.authorMantel, I-
dc.contributor.authorGelize, E-
dc.contributor.authorLi, X-
dc.contributor.authorXie, X-
dc.contributor.authorArboleda, A-
dc.contributor.authorSeminel, M-
dc.contributor.authorLevy-Boukris, R-
dc.contributor.authorDernigoghossian, M-
dc.contributor.authorPrunotto, A-
dc.contributor.authorAndrieu-Soler, C-
dc.contributor.authorRivolta, C-
dc.contributor.authorCanonica, J-
dc.contributor.authorNaud, M-C-
dc.contributor.authorLechner, S-
dc.contributor.authorFarman, N-
dc.contributor.authorBravo-Osuna, I-
dc.contributor.authorHerrero-Vanrell, R-
dc.contributor.authorJaisser, F-
dc.contributor.authorBehar-Cohen, F-
dc.date.accessioned2019-08-20T11:45:11Z-
dc.date.available2019-08-20T11:45:11Z-
dc.date.issued2019-01-21-
dc.identifier.citationNature Communications, 2019, volume 10, Article number: 369en
dc.identifier.urihttps://www.nature.com/articles/s41467-018-08125-6en
dc.identifier.urihttp://hdl.handle.net/2381/45279-
dc.descriptionAll relevant data are available from the corresponding author upon reasonable request. RNA-sequencing data are available from ArrayExpress database at EMBL-EBI under accession number E-MTAB-7438. The images from figures are available at figshare https://figshare.com/articles/Antagonism_of_the_mineralocorticoid_pathway_limits_choroidal_neovascularization/7283648 . A Reporting Summary for this Article is available as a Supplementary Information file.en
dc.description.abstractChoroidal neovascularization (CNV) is a major cause of visual impairment in patients suffering from wet age-related macular degeneration (AMD), particularly when refractory to intraocular anti-VEGF injections. Here we report that treatment with the oral mineralocorticoid receptor (MR) antagonist spironolactone reduces signs of CNV in patients refractory to anti-VEGF treatment. In animal models of wet AMD, pharmacological inhibition of the MR pathway or endothelial-specific deletion of MR inhibits CNV through VEGF-independent mechanisms, in part through upregulation of the extracellular matrix protein decorin. Intravitreal injections of spironolactone-loaded microspheres and systemic delivery lead to similar reductions in CNV. Together, our work suggests MR inhibition as a novel therapeutic option for wet AMD patients unresponsive to anti-VEGF drugs.en
dc.description.sponsorshipWe thank INSERM, the Agence Nationale de la Recherche (ANR Mineraloret ANR-11-BSV1–0022, and ROCK-SUR-MeR ANR-15-CE18–0032), the Fondation pour la Recherche Médicale (FRM Visual System 2013, DVS20131228894) and the Swiss National Science Foundation (grant #156260 to C. R.) for financial support. This research was also supported by grants from MAT2013–43127- R and MAT2017–83858-C2–1 MINECO/AEI/FEDER, UE. We thank Christophe Klein from Center d’Histologie, d’Imagerieet de Cytométrie, and Georges Zadigue from Center d’Explorations Fonctionnelles of Center de Recherche des Cordeliers for their technical support. We thank Maëva Dupuis-Deniaud, MDSTAT Consulting Lyon, France for her assistance in the statistical analysis.en
dc.language.isoenen
dc.publisherNature Research (part of Springer Nature)en
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/30664640-
dc.rightsCopyright © the authors, 2019. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectAgeden
dc.subjectAged, 80 and overen
dc.subjectAngiogenesis Inhibitorsen
dc.subjectAnimalsen
dc.subjectChoroiden
dc.subjectChoroidal Neovascularizationen
dc.subjectDrug Compoundingen
dc.subjectFemaleen
dc.subjectGene Expressionen
dc.subjectHumansen
dc.subjectIntravitreal Injectionsen
dc.subjectMacular Degenerationen
dc.subjectMaleen
dc.subjectMiceen
dc.subjectMice, Transgenicen
dc.subjectMicrospheresen
dc.subjectMineralocorticoid Receptor Antagonistsen
dc.subjectPilot Projectsen
dc.subjectProspective Studiesen
dc.subjectRanibizumaben
dc.subjectRats, Long-Evansen
dc.subjectReceptors, Mineralocorticoiden
dc.subjectReceptors, Vascular Endothelial Growth Factoren
dc.subjectRecombinant Fusion Proteinsen
dc.subjectSpironolactoneen
dc.subjectTreatment Outcomeen
dc.subjectVascular Endothelial Growth Factor Aen
dc.titleMineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration.en
dc.typeJournal Articleen
dc.identifier.doi10.1038/s41467-018-08125-6-
dc.identifier.eissn2041-1723-
dc.identifier.pii10.1038/s41467-018-08125-6-
dc.description.statusPeer-revieweden
dc.description.versionPublisher Versionen
dc.type.subtypeJournal Article;Research Support, Non-U.S. Gov't-
pubs.organisational-group/Organisationen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCESen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciencesen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Genetics and Genome Biologyen
dc.dateaccepted2018-12-11-
Appears in Collections:Published Articles, Dept. of Genetics



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