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

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 <i>KEAP1/Nrf2</i> complex, along with the expression of <i>phosphoinositide 3-kinase (PI3K)</i> and <i>protein kinase B (AKT)</i>, increased in the coculture group compared with the H₂O₂ treatment group (<i>* p</i> < 0.05). The expression levels of antioxidant genes increased in the cocultured group compared with those in the H₂O₂ treatment group (* <i>p</i> < 0.05), whereas the ROS levels decreased in the cocultured group (* <i>p</i> < 0.05). Additionally, both the expression of mitochondrial dynamics markers and the mitochondrial membrane potential increased when the cells were cocultured with PD-MSCs (* <i>p</i> < 0.05). PD-MSC cocultivation decreased the expression levels of lipoproteins (* <i>p</i> < 0.05). Finally, we confirmed that PD-MSCs promoted the expression of RPE-specific genes in H₂O₂-injured ARPE-19 cells (<i>* p</i> < 0.05). These findings suggest a new aspect of stem cell treatment for AMD induced by oxidative stress.