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Journal Articles American Journal of Translational Research Year : 2020

The antidiabetic drug glibenclamide exerts direct retinal neuroprotection

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Marianne Berdugo
  • Function : Author
  • PersonId : 1080183
Justine Guegan
  • Function : Author
  • PersonId : 1080184
Émilie Picard
Lolita Radet
  • Function : Author
  • PersonId : 1080185
Alejandra Daruich
Patricia Crisanti
  • Function : Author
  • PersonId : 839991

Abstract

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.
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Dates and versions

inserm-02980520 , version 1 (27-10-2020)

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Marianne Berdugo, Kimberley Delaunay, Marie-Christine Naud, Justine Guegan, Alexandre Moulin, et al.. The antidiabetic drug glibenclamide exerts direct retinal neuroprotection: Glibenclamide exerts retinal neuroprotection. American Journal of Translational Research, 2020, pp.S1931-5244(20)30244-9. ⟨10.1016/j.trsl.2020.10.003⟩. ⟨inserm-02980520⟩
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