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

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  • Min Zhao

    (Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
    Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
    Paris Descartes University, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers)

  • Irmela Mantel

    (University of Lausanne, Jules Gonin Eye Hospital, Fondation Asile des Aveugles)

  • Emmanuelle Gelize

    (Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
    Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
    Paris Descartes University, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers)

  • Xinxin Li

    (Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
    Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
    Paris Descartes University, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers)

  • Xiaoyue Xie

    (Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
    Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
    Paris Descartes University, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers)

  • Alejandro Arboleda

    (Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
    Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
    Paris Descartes University, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers
    University of Miami Miller School of Medicine)

  • Marie Seminel

    (Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
    Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
    Paris Descartes University, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers)

  • Rinath Levy-Boukris

    (Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
    Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
    Paris Descartes University, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers)

  • Marilyn Dernigoghossian

    (Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
    Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
    Paris Descartes University, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers)

  • Andrea Prunotto

    (University of Lausanne)

  • Charlotte Andrieu-Soler

    (IGMM, CNRS, Univ. Montpellier)

  • Carlo Rivolta

    (University of Lausanne
    University of Leicester)

  • Jérémie Canonica

    (University of Lausanne, Jules Gonin Eye Hospital, Fondation Asile des Aveugles)

  • Marie-Christine Naud

    (Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
    Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
    Paris Descartes University, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers)

  • Sebastian Lechner

    (Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
    Paris Descartes University, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers
    Inserm UMR_S 1138, Team 1, Centre de Recherche des Cordeliers)

  • Nicolette Farman

    (Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
    Paris Descartes University, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers
    Inserm UMR_S 1138, Team 1, Centre de Recherche des Cordeliers)

  • Irene Bravo-Osuna

    (Universidad Complutense de Madrid
    Instituto Universitario de Farmacia Industrial, Faculty of Pharmacy, Universidad Complutense de Madrid
    Fundación para la Investigación-HCSC, Instituto de Investigación Sanitaria San Carlos (IdISSC))

  • Rocio Herrero-Vanrell

    (Universidad Complutense de Madrid
    Instituto Universitario de Farmacia Industrial, Faculty of Pharmacy, Universidad Complutense de Madrid
    Fundación para la Investigación-HCSC, Instituto de Investigación Sanitaria San Carlos (IdISSC))

  • Frederic Jaisser

    (Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
    Paris Descartes University, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers
    Inserm UMR_S 1138, Team 1, Centre de Recherche des Cordeliers)

  • Francine Behar-Cohen

    (Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
    Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
    Paris Descartes University, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers
    Assistance Publique - Hôpitaux de Paris, Hôtel-Dieu de Paris)

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.

Suggested Citation

  • Min Zhao & Irmela Mantel & Emmanuelle Gelize & Xinxin Li & Xiaoyue Xie & Alejandro Arboleda & Marie Seminel & Rinath Levy-Boukris & Marilyn Dernigoghossian & Andrea Prunotto & Charlotte Andrieu-Soler , 2019. "Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08125-6
    DOI: 10.1038/s41467-018-08125-6
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