Nrf2 Activated by PD-MSCs Attenuates Oxidative Stress in a Hydrogen Peroxide-Injured Retinal Pigment Epithelial Cell Line

TL;DR

Stem cells from the placenta reduce oxidative stress in retinal cells, suggesting a new treatment for age-related macular degeneration.

Contribution

PD-MSCs were shown to activate Nrf2 and reduce oxidative stress in retinal pigment epithelial cells.

Findings

PD-MSC coculture increased antioxidant gene expression and decreased ROS levels in H2O2-injured cells.

Mitochondrial function improved in cells cocultured with PD-MSCs.

PD-MSCs promoted RPE-specific gene expression in injured retinal cells.

Abstract

Age-related macular degeneration (AMD) is a retinal degenerative disease caused by oxidative stress. Thus, we aimed to reduce oxidative stress through the use of placenta-derived mesenchymal stem cells (PD-MSCs). To induce oxidative stress in ARPE-19 cells, we treated them with 200 µM hydrogen peroxide (H2O2) for 2 h and then cocultured them with PD-MSCs. The dissociation of the KEAP1/Nrf2 complex, along with the expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), increased in the coculture group compared with the H2O2 treatment group (* p < 0.05). The expression levels of antioxidant genes increased in the cocultured group compared with those in the H2O2 treatment group (* p < 0.05), whereas the ROS levels decreased in the cocultured group (* p < 0.05). Additionally, both the expression of mitochondrial dynamics markers and the mitochondrial membrane potential increased when the cells were cocultured with PD-MSCs (* p < 0.05). PD-MSC cocultivation decreased the expression levels of lipoproteins (* p < 0.05). Finally, we confirmed that PD-MSCs promoted the expression of RPE-specific genes in H2O2-injured ARPE-19 cells (* p < 0.05). These findings suggest a new aspect of stem cell treatment for AMD induced by oxidative stress.

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