Memantine, Simvastatin, and Epicatechin Inhibit 7-Ketocholesterol-induced Apoptosis in Retinal Pigment Epithelial Cells But Not Neurosensory Retinal Cells In Vitro.
7-Ketocholesterol
Memantine
Epicatechin
Journal
Journal of ophthalmic & vision research
ISSN: 2008-2010
Titre abrégé: J Ophthalmic Vis Res
Pays: United Arab Emirates
ID NLM: 101497643
Informations de publication
Date de publication:
Historique:
received:
20
03
2020
accepted:
21
06
2020
entrez:
2
11
2020
pubmed:
3
11
2020
medline:
3
11
2020
Statut:
epublish
Résumé
7-ketocholesterol (7kCh), a natural byproduct of oxidation in lipoprotein deposits is implicated in the pathogenesis of diabetic retinopathy and age-related macular degeneration (AMD). This study was performed to investigate whether several clinical drugs can inhibit 7kCh-induced caspase activation and mitigate its apoptotic effects on retinal cells in vitro. Two populations of retinal cells, human retinal pigment epithelial cells (ARPE-19) and rat neuroretinal cells (R28) were exposed to 7kCh in the presence of the following inhibitors: Z-VAD-FMK (pan-caspase inhibitor), simvastatin, memantine, epicatechin, and Z-IETD-FMK (caspase-8 inhibitor) or Z-ATAD-FMK (caspase-12 inhibitor). Caspase-3/7, -8, and -12 activity levels were measured by fluorochrome caspase assays to quantify cell death. IncuCyte live-cell microscopic images were obtained to quantify cell counts. Exposure to 7kCh for 24 hours significantly increased caspase activities for both ARPE-19 and R28 cells ( Several current drugs protect ARPE-19 cells but not R28 cells from 7kCh-induced apoptosis, suggesting that a multiple-drug approach is needed to protect both cells types in various retinal diseases.
Identifiants
pubmed: 33133437
doi: 10.18502/jovr.v15i4.7781
pmc: PMC7591846
doi:
Types de publication
Journal Article
Langues
eng
Pagination
470-480Subventions
Organisme : NEI NIH HHS
ID : R01 EY027363
Pays : United States
Informations de copyright
Copyright © 2020 Neekhra et al.
Déclaration de conflit d'intérêts
There are no conflicts of interest.
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