• Marianne Berdugo, Kimberley Delaunay, Marie-Christine Naud, Justine Guegan, Alexandre Moulin, Michèle Savoldelli, Emilie Picard, Lolita Radet, Laurent Jonet, Zoubir Djerada, Claire Gozalo, Alejandra Daruich, Jacques Beltrand, Jean-Claude Jeanny, Elsa Kermorvant-Duchemin, Patricia Crisanti, Michel Polak, and Francine Behar-Cohen.
• Université de Paris, Faculté de Santé, Paris, France; Inserm UMRS 1138, Team 17: Physiopathology of Ocular Diseases-Therapeutic Innovations, Centre de Recherche des Cordeliers, Paris, France; Sorbonne Université, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France.
• Transl Res. 2021 Mar 1; 229: 839983-99.

AbstractSulfonylureas, widely used as hypoglycemic agents in adults with type 2 diabetes, have neuroprotective effects in preclinical models of central nervous system injury, and in children with neuropsychomotor impairments linked to neonatal diabetes secondary to ATP-sensitive potassium channel mutations. In the human and rodent retina, we show that the glibenclamide-activated channel sulfonylurea receptor 1 (SUR1) is expressed in the retina and enriched in the macula; we also show that it colocalizes with the potassium channel Kir6.2, and with the cation channel transporter TRPM4. Glibenclamide (glyburide), administered at doses that did not decrease the glycemia, or injected directly into the eye, protected the structure and the function of the retina in various models of retinal injury that recapitulate the pathogenic neurodegenerative events in the diabetic retina. The downregulation of SUR1 using a siRNA suppressed the neuroprotective effects of glibenclamide on excitotoxic stress-induced cell death. The glibenclamide effects include the transcriptional regulation of antioxidant and neuroprotective genes. Ocular glibenclamide could be repurposed for diabetic retinopathy.Copyright © 2020. Published by Elsevier Inc.

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