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

Authors :
Picard, Emilie
Youale, Jenny
Hyman, Max J.
Xie, Edward
Achiedo, Seiki
Kaufmann, Gabriel T.
Moir, John
Daruich, Alejandra
Crisanti, Patricia
Torriglia, Alicia
Polak, Michel
Behar-Cohen, Francine
Skondra, Dimitra
Berdugo, Marianne
Source :
Translational Research: The Journal of Laboratory & Clinical Medicine; Oct2024, Vol. 272, p81-94, 14p
Publication Year :
2024

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19315244
Volume :
272
Database :
Supplemental Index
Journal :
Translational Research: The Journal of Laboratory & Clinical Medicine
Publication Type :
Academic Journal
Accession number :
179465482
Full Text :
https://doi.org/10.1016/j.trsl.2024.05.002