RESEARCH ARTICLE
The GPCR Antagonistic Drug CM-20 Stimulates Mitochondrial Activity in Human RPE Cells
Qing Chang1, *, Siquan Chen2, Tahua Yang1
Article Information
Identifiers and Pagination:
Year: 2022Volume: 16
E-location ID: e1874091X2206270
Publisher ID: e1874091X2206270
DOI: 10.2174/1874091X-v16-e2206270
Article History:
Received Date: 20/10/2021Revision Received Date: 28/2/2022
Acceptance Date: 17/3/2022
Electronic publication date: 22/08/2022
Collection year: 2022
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background:
Mitochondrial dysfunction in retinal pigment epithelium (RPE) is a pathogenic factor in age-related macular degeneration (AMD). Improvement of mitochondrial function may ameliorate RPE bioenergetics status, which may in turn nourish the retinal photoreceptors against degenerative loss.
Objective:
The purpose of this study is to examine the G-protein coupled receptor (GPCR) antagonistic drug CM-20 in modulating mitochondrial function in RPE cells.
Methods:
Human-derived ARPE-19 cell line was differentiated to improve RPE morphology. Dose response of CM-20 was performed to examine mitochondrial membrane potential (MMP). Secondary validation with multiplexed live-cell mitochondrial imaging was performed. Protection of CM-20 to mitochondria against oxidative stress was detected under co-treatment with hydrogen peroxide.
Results:
Treatment with CM-20 elicited a dose-dependent increase of MMP. Multiplexed live-cell mitochondrial imaging showed consistent increase of MMP at an optimal concentration of CM-20 (12.5 µM). MMP was significantly reduced under hydrogen peroxide-induced oxidative stress and treatment with CM-20 showed rescue effects to MMP.
Conclusion:
CM-20 increases mitochondrial function and protects mitochondria under oxidative stress. As both GPCRs and mitochondria are potential drug targets, retinal neuroprotective testing of CM-20 is warranted in animal models of retinal degeneration.
