The antidiabetic drug glibenclamide exerts direct retinal neuroprotection
Autor: | Claire Gozalo, Laurent Jonet, Francine Behar-Cohen, Patricia Crisanti, Michèle Savoldelli, Zoubir Djerada, Elsa Kermorvant-Duchemin, Emilie Picard, Jacques Beltrand, Alexandre Moulin, Jean-Claude Jeanny, Alejandra Daruich, Justine Guegan, Lolita Radet, Kimberley Delaunay, Michel Polak, Marie-Christine Naud, Marianne Berdugo |
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Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine genetic structures Administration Oral Pharmacology Sulfonylurea Receptors Glibenclamide 0302 clinical medicine Chlorocebus aethiops Glyburide Medicine General Medicine Diabetic retinopathy Middle Aged Potassium channel 3. Good health Neuroprotective Agents medicine.anatomical_structure 030220 oncology & carcinogenesis Female Retinal Neurons medicine.drug endocrine system Central nervous system TRPM Cation Channels Neuroprotection Diabetes Mellitus Experimental 03 medical and health sciences Retinal Diseases Downregulation and upregulation Physiology (medical) Animals Humans Hypoglycemic Agents Potassium Channels Inwardly Rectifying Rats Wistar Retina Diabetic Retinopathy business.industry Biochemistry (medical) Public Health Environmental and Occupational Health medicine.disease eye diseases Macaca fascicularis 030104 developmental biology Rats Inbred Lew Hyperglycemia Sulfonylurea receptor sense organs business |
Zdroj: | Translational Research. 229:83-99 |
ISSN: | 1931-5244 |
Popis: | Sulfonylureas, 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. |
Databáze: | OpenAIRE |
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