Airborne Exposure of the Cornea to PM(10) Induces Oxidative Stress and Disrupts Nrf2 Mediated Anti-Oxidant Defenses

The purpose of this study is to test the effects of whole-body animal exposure to airborne particulate matter (PM) with an aerodynamic diameter of <10 μm (PM(10)) in the mouse cornea and in vitro. C57BL/6 mice were exposed to control or 500 µg/m(3) PM(10) for 2 weeks. In vivo, reduced glutathione (GSH) and malondialdehyde (MDA) were analyzed. RT-PCR and ELISA evaluated levels of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and inflammatory markers. SKQ1, a novel mitochondrial antioxidant, was applied topically and GSH, MDA and Nrf2 levels were tested. In vitro, cells were treated with PM(10) ± SKQ1 and cell viability, MDA, mitochondrial ROS, ATP and Nrf2 protein were tested. In vivo, PM(10) vs. control exposure significantly reduced GSH, corneal thickness and increased MDA levels. PM(10)-exposed corneas showed significantly higher mRNA levels for downstream targets, pro-inflammatory molecules and reduced Nrf2 protein. In PM(10)-exposed corneas, SKQ1 restored GSH and Nrf2 levels and lowered MDA. In vitro, PM(10) reduced cell viability, Nrf2 protein, and ATP, and increased MDA, and mitochondrial ROS; while SKQ1 reversed these effects. Whole-body PM(10) exposure triggers oxidative stress, disrupting the Nrf2 pathway. SKQ1 reverses these deleterious effects in vivo and in vitro, suggesting applicability to humans.