Dimethyl Fumarate Protects Retinal Pigment Epithelium from Blue Light-Induced Oxidative Damage via the Nrf2 Pathway
Hideyuki Shimizu1, Kei Takayama2, Kazuhisa Yamada1
1Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Abstract:
The purpose of this study is to investigate the protective effect of dimethyl fumarate (DMF), the methyl-ester of fumaric acid, against blue-light (BL) exposure in retinal pigment epithelial (RPE) cells. ARPE-19 cells, a human RPE cell line, were cultured with DMF followed by exposure to BL. Reactive oxygen species (ROS) generation, cell viability, and cell death rate were determined. Real-time polymerase chain reaction and Western blotting were performed to determine the change in nuclear factor (erythroid-derived)-like 2 (NRF2) expression. Twenty-seven inflammatory cytokines in the supernatant of culture medium were measured. BL exposure induced ROS generation in ARPE-19 cells, which DMF alleviated in a concentration-dependent manner. BL exposure increased the ARPE-19 cell death rate, which DMF alleviated. BL exposure induced ARPE-19 cell apoptosis, again alleviated by DMF. Under BL exposure, DMF increased the NRF2 mRNA level and promoted NRF2 expression in the nucleus. BL also strongly increased interleukin (IL)-1β and fibroblast growth factor (FGF) expression. BL strongly induced RPE cell damage with apoptotic change while DMF mainly reduced inflammation in BL-induced RPE damage, resulting in blockade of cell death. DMF has a protective effect in RPE cells against BL exposure via activation of the NRF2 pathway.
Insights
Dimethyl fumarate (DMF) protects retinal pigment epithelial (RPE) cells from blue-light (BL) damage. DMF reduces reactive oxygen species and inflammation by activating the NRF2 pathway, preventing cell death.
Area of Science:
- Ophthalmology
- Cell Biology
- Toxicology
Background:
- Blue-light (BL) exposure is a risk factor for retinal damage.
- Retinal pigment epithelial (RPE) cells are crucial for retinal health and susceptible to BL-induced injury.
- Understanding protective mechanisms against BL damage is vital for preventing vision loss.
Purpose of the Study:
- To investigate the protective effects of dimethyl fumarate (DMF) against BL-induced damage in RPE cells.
- To elucidate the role of the NRF2 pathway in DMF's protective mechanism.
- To assess DMF's impact on oxidative stress, inflammation, and cell viability.
Main Methods:
- ARPE-19 human RPE cells were treated with DMF and exposed to BL.
- Assessed reactive oxygen species (ROS) generation, cell viability, and apoptosis.
- Utilized real-time PCR and Western blotting to analyze NRF2 expression.
- Measured inflammatory cytokine levels in cell culture supernatant.
Main Results:
- DMF alleviated BL-induced ROS generation in a concentration-dependent manner.
- DMF reduced BL-induced RPE cell death and apoptosis.
- DMF upregulated NRF2 mRNA and protein expression, promoting nuclear translocation.
- DMF significantly reduced BL-induced inflammatory cytokines, including IL-1β and FGF.
Conclusions:
- Dimethyl fumarate (DMF) demonstrates significant protective effects against blue-light (BL) induced RPE cell damage.
- DMF exerts its protective effects primarily by activating the NRF2 pathway, which mitigates oxidative stress and inflammation.
- These findings suggest DMF as a potential therapeutic agent for preventing or treating conditions associated with BL exposure and RPE damage.
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