• Transl Res · Oct 2024

    Glyburide confers neuroprotection against age-related macular degeneration (AMD).

    • Emilie Picard, Jenny Youale, Max J Hyman, Edward Xie, Seiki Achiedo, Gabriel T Kaufmann, John Moir, Alejandra Daruich, Patricia Crisanti, Alicia Torriglia, Michel Polak, Francine Behar-Cohen, Dimitra Skondra, and Marianne Berdugo.
    • Inserm UMRS1138, Team 1: 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; Université Paris Cité, Faculté de Santé, Paris, France.
    • Transl Res. 2024 Oct 1; 272: 819481-94.

    AbstractGlyburide, a sulfonylurea drug used to treat type 2 diabetes, boasts neuroprotective effects by targeting the sulfonylurea receptor 1 (SUR1) and associated ion channels in various cell types, including those in the central nervous system and the retina. Previously, we demonstrated that glyburide therapy improved retinal function and structure in a rat model of diabetic retinopathy. In the present study, we explore the application of glyburide in non-neovascular ("dry") age-related macular degeneration (AMD), another progressive disease characterized by oxidative stress-induced damage and neuroinflammation that trigger cell death in the retina. We show that glyburide administration to a human cone cell line confers protection against oxidative stress, inflammasome activation, and apoptosis. To corroborate our in vitro results, we also conducted a case-control study, controlling for AMD risk factors and other diabetes medications. It showed that glyburide use in patients reduces the odds of new-onset dry AMD. A positive dose-response relationship is observed from this analysis, in which higher cumulative doses of glyburide further reduce the odds of new-onset dry AMD. In the quest for novel therapies for AMD, glyburide emerges as a promising repurposable drug given its known safety profile. The results from this study provide insights into the multifaceted actions of glyburide and its potential as a neuroprotective agent for retinal diseases; however, further preclinical and clinical studies are needed to validate its therapeutic potential in the context of degenerative retinal disorders such as AMD.Copyright © 2024. Published by Elsevier Inc.

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