Mineralocorticoid Receptor Pathway and Its Antagonism in a Model of Diabetic Retinopathy
| Autor: | Alexandre Moulin, Rinath Levy, Francine Behar-Cohen, Emmanuelle Gelize, Kimberley Delaunay, F. Azan, Min Zhao, Irene Bravo-Osuna, Marie-Christine Naud, Rocío Herrero-Vanrell, Justine Guegan, Patricia Lassiaz, Eric Pussard, Marianne Berdugo |
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| Přispěvatelé: | Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université de Lausanne = University of Lausanne (UNIL), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Physiologie et physiopathologie endocriniennes (PHYSENDO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Gestionnaire, HAL Sorbonne Université 5 |
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Hydrocortisone medicine.drug_class Endocrinology Diabetes and Metabolism Spironolactone Retina Diabetic nephropathy chemistry.chemical_compound Mineralocorticoid receptor Polylactic Acid-Polyglycolic Acid Copolymer Internal medicine Diabetes mellitus Internal Medicine medicine Animals Humans Mineralocorticoid Receptor Antagonists [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Diabetic Retinopathy business.industry Rats Inbred Strains Diabetic retinopathy [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism medicine.disease Rats Up-Regulation Vitreous Body Endocrinology medicine.anatomical_structure Receptors Mineralocorticoid chemistry Diabetes Mellitus Type 2 Gene Expression Regulation Mineralocorticoid Delayed-Action Preparations Female business Retinopathy Retinal Neurons |
| Zdroj: | Diabetes Diabetes, 2021, 70 (11), pp.2668-2682. ⟨10.2337/db21-0099⟩ |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db21-0099⟩ |
| Popis: | Diabetic retinopathy remains a major cause of vision loss worldwide. Mineralocorticoid receptor (MR) pathway activation contributes to diabetic nephropathy but its role in retinopathy is unknown. In this study, we show that MR is overexpressed in the retina of type 2 diabetic Goto-Kakizaki (GK) rats and humans and, that cortisol is the MR ligand in human eyes. Lipocalin 2 and galectin 3, two biomarkers of diabetic complications regulated by MR are increased in GK and human retina. The sustained intraocular delivery of spironolactone, a steroidal mineralocorticoid antagonist, decreased the early and late pathogenic features of retinopathy in GK rats, such as retinal inflammation, vascular leakage and retinal edema through the up-regulation of genes encoding proteins known to intervene in vascular permeability such as Hey1, Vldlr, Pten, Slc7a1, Tjp1, Dlg1 and Sesn2 but did not decrease VEGF. Spironolactone also normalized the distribution of ion and water channels in macroglial cells. These results indicate that MR is activated in GK and human diabetic retina and that local MR antagonism could be a novel therapeutic option for diabetic retinopathy. |
| Databáze: | OpenAIRE |
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