RESEARCH ARTICLE


The GPCR Antagonistic Drug CM-20 Stimulates Mitochondrial Activity in Human RPE Cells



Qing Chang1, *, Siquan Chen2, Tahua Yang1
1 University of Illinois Technology Innovation Lab and Argos Vision Inc., Chicago, United States
2 Cellular Screening Center, The University of Chicago, Chicago, United States


Article Metrics

CrossRef Citations:
0
Total Statistics:

Full-Text HTML Views: 243
Abstract HTML Views: 72
PDF Downloads: 166
Total Views/Downloads: 507
Unique Statistics:

Full-Text HTML Views: 169
Abstract HTML Views: 58
PDF Downloads: 106
Total Views/Downloads: 356



Creative Commons License
© 2022 Chang et al.

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.

* Address correspondence to this author University of Illinois Technology Innovation Lab/Argos Vision Inc., 2242 W Harrison St, Suite 201, Chicago, IL 60612, United States; E-mail: changq@uic.edu


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.

Keywords: GPCR, Mitochondria, Polypharmacology, Multi-target drug, RPE, Oxidative stress, Age-related macular degeneration (AMD).