Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration.

Details

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State: Public
Version: Final published version
Serval ID
serval:BIB_C7716BDC7511
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration.
Journal
Nature communications
Author(s)
Zhao M., Mantel I., Gelize E., Li X., Xie X., Arboleda A., Seminel M., Levy-Boukris R., Dernigoghossian M., Prunotto A., Andrieu-Soler C., Rivolta C., Canonica J., Naud M.C., Lechner S., Farman N., Bravo-Osuna I., Herrero-Vanrell R., Jaisser F., Behar-Cohen F.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
21/01/2019
Peer-reviewed
Oui
Volume
10
Number
1
Pages
369
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Choroidal 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.
Keywords
Aged, Aged, 80 and over, Angiogenesis Inhibitors/therapeutic use, Animals, Choroid/drug effects, Choroid/metabolism, Choroid/pathology, Choroidal Neovascularization/drug therapy, Choroidal Neovascularization/genetics, Choroidal Neovascularization/metabolism, Choroidal Neovascularization/pathology, Drug Compounding/methods, Female, Gene Expression, Humans, Intravitreal Injections, Macular Degeneration/drug therapy, Macular Degeneration/genetics, Macular Degeneration/metabolism, Macular Degeneration/pathology, Male, Mice, Mice, Transgenic, Microspheres, Mineralocorticoid Receptor Antagonists/therapeutic use, Pilot Projects, Prospective Studies, Ranibizumab/therapeutic use, Rats, Long-Evans, Receptors, Mineralocorticoid/genetics, Receptors, Mineralocorticoid/metabolism, Receptors, Vascular Endothelial Growth Factor/therapeutic use, Recombinant Fusion Proteins/therapeutic use, Spironolactone/therapeutic use, Treatment Outcome, Vascular Endothelial Growth Factor A/antagonists & inhibitors, Vascular Endothelial Growth Factor A/genetics, Vascular Endothelial Growth Factor A/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
31/01/2019 9:00
Last modification date
20/08/2019 16:42
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