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
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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