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

Autor: Picard E; 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., Youale J; 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., Hyman MJ; enter for Health and the Social Sciences, University of Chicago, Chicago, Illinois., Xie E; Stony Brook University Hospital, Stony Brook, NY., Achiedo S; 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., Kaufmann GT; Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio., Moir J; Pritzker School of Medicine, University of Chicago, Chicago, Illinois., Daruich A; 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; AP-HP, Service d'Ophtalmologie, Hôpital universitaire Necker-Enfants Malades, Paris, France., Crisanti P; 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., Torriglia A; 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., Polak M; AP-HP, Service d'endocrinologie, diabétologie et gynécologie pédiatriques, Hôpital universitaire Necker-Enfants Malades, Paris, France; Inserm U1016, Institut Cochin, Paris, France; Inserm UMR 1163, Institut Imagine, Université Paris Cité, Paris, France., Behar-Cohen F; 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; AP-HP, OphtalmoPôle, Hôpital Cochin, Department of Ophthalmology and Visual Science, Paris, France. Electronic address: francine.behar@gmail.com., Skondra D; Department of Ophthalmology and Visual Science, University of Chicago, Chicago, Illinois., Berdugo M; 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.
Jazyk: angličtina
Zdroj: Translational research : the journal of laboratory and clinical medicine [Transl Res] 2024 Oct; Vol. 272, pp. 81-94. Date of Electronic Publication: 2024 May 29.
DOI: 10.1016/j.trsl.2024.05.002
Abstrakt: Glyburide, 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.)
Databáze: MEDLINE
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