The antidiabetic drug glibenclamide exerts direct retinal neuroprotection.

The antidiabetic drug glibenclamide exerts direct retinal neuroprotection. Transl Res. 2020 Oct 17;: Authors: Berdugo M, Delaunay K, Naud MC, Guegan J, Moulin A, Savoldelli M, Picard E, Radet L, Jonet L, Djerada Z, Gozalo C, Daruich A, Beltrand J, Jeanny JC, Kermorvant-Duchemin E, Crisanti P, Polak M, Behar-Cohen F Abstract Sulfonylureas, widely used as hypoglycaemic 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 SUR1 is expressed in the retina and enriched in the macula; we also show that it co-localizes with the potassium channel Kir6.2, and with the cation channel transporter TRPM4. Glibenclamide (glyburide), administered at doses that did not decrease the glycaemia, 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 down-regulation 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 anti-oxidant and neuroprotective genes. Ocular glibenclamide could be ...
Source: Translational Research : the journal of laboratory and clinical medicine - Category: Laboratory Medicine Authors: Tags: Transl Res Source Type: research