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.