Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration.
Aged
Aged, 80 and over
Angiogenesis Inhibitors
/ therapeutic use
Animals
Choroid
/ drug effects
Choroidal Neovascularization
/ drug therapy
Drug Compounding
/ methods
Female
Gene Expression
Humans
Intravitreal Injections
Macular Degeneration
/ drug therapy
Male
Mice
Mice, Transgenic
Microspheres
Mineralocorticoid Receptor Antagonists
/ therapeutic use
Pilot Projects
Prospective Studies
Ranibizumab
/ therapeutic use
Rats, Long-Evans
Receptors, Mineralocorticoid
/ genetics
Receptors, Vascular Endothelial Growth Factor
/ therapeutic use
Recombinant Fusion Proteins
/ therapeutic use
Spironolactone
/ therapeutic use
Treatment Outcome
Vascular Endothelial Growth Factor A
/ antagonists & inhibitors
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 01 2019
21 01 2019
Historique:
received:
30
03
2018
accepted:
11
12
2018
entrez:
22
1
2019
pubmed:
22
1
2019
medline:
6
2
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30664640
doi: 10.1038/s41467-018-08125-6
pii: 10.1038/s41467-018-08125-6
pmc: PMC6341116
doi:
Substances chimiques
Angiogenesis Inhibitors
0
Mineralocorticoid Receptor Antagonists
0
Receptors, Mineralocorticoid
0
Recombinant Fusion Proteins
0
VEGFA protein, human
0
Vascular Endothelial Growth Factor A
0
aflibercept
15C2VL427D
Spironolactone
27O7W4T232
Receptors, Vascular Endothelial Growth Factor
EC 2.7.10.1
Ranibizumab
ZL1R02VT79
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
369Subventions
Organisme : NCCIH NIH HHS
ID : F05 AT002013
Pays : United States
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