caa a22 4500 555159639 CHVBK 20190327044941.0 cr unu---uuuuu 190202e20190121xx s 000 0 eng 10.1038/s41467-018-08125-6 doi (SERVAL)BIB_C7716BDC7511 30664640 pmid 000456165100006 isiid Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration [Elektronische Daten] [M. Zhao, I. Mantel, E. Gelize, X. Li, X. Xie, A. Arboleda, M. Seminel, R. Levy-Boukris, M. Dernigoghossian, A. Prunotto, C. Andrieu-Soler, C. Rivolta, J. Canonica, M.C. Naud, S. Lechner, N. Farman, I. Bravo-Osuna, R. Herrero-Vanrell, F. Jaisser, F. Behar-Cohen] 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. Zhao M. aut Mantel I. aut Gelize E. aut Li X. aut Xie X. aut Arboleda A. aut Seminel M. aut Levy-Boukris R. aut Dernigoghossian M. aut Prunotto A. aut Andrieu-Soler C. aut Rivolta C. aut Canonica J. aut Naud M.C. aut Lechner S. aut Farman N. aut Bravo-Osuna I. aut Herrero-Vanrell R. aut Jaisser F. aut Behar-Cohen F. aut Nature communications 10/1(2019-01-21), 369 10:1<369 2019 10 1 article serval SERVAL 700 1- Zhao M. aut SERVAL 700 1- Mantel I. aut SERVAL 700 1- Gelize E. aut SERVAL 700 1- Li X. aut SERVAL 700 1- Xie X. aut SERVAL 700 1- Arboleda A. aut SERVAL 700 1- Seminel M. aut SERVAL 700 1- Levy-Boukris R. aut SERVAL 700 1- Dernigoghossian M. aut SERVAL 700 1- Prunotto A. aut SERVAL 700 1- Andrieu-Soler C. aut SERVAL 700 1- Rivolta C. aut SERVAL 700 1- Canonica J. aut SERVAL 700 1- Naud M.C. aut SERVAL 700 1- Lechner S. aut SERVAL 700 1- Farman N. aut SERVAL 700 1- Bravo-Osuna I. aut SERVAL 700 1- Herrero-Vanrell R. aut SERVAL 700 1- Jaisser F. aut SERVAL 700 1- Behar-Cohen F. aut SERVAL 773 0- Nature communications 10/1(2019-01-21), 369 10:1<369 2019 10 BK010053 XK010053 XK010000 SERVAL SERVAL SERVAL article