Cellular responses of human Muller glia exposed to test dust pollution

Air pollution is a global environmental hazard and is associated with increased severity and progression of several retinal diseases, including glaucoma and age-related macular degeneration. Muller glia are radial glia in the retina that play essential roles in metabolic support, redox balance and neuroprotection. Despite their importance, the effects of pollution on retinal glial responses are not well characterized. The objectives of this study were to determine the effects of a test dust preparation on viability, injury responses and oxidative stress levels in human Muller glia cell line. Arizona test dust (ATD) contains silica, oxides, particulate matter smaller than 10 μm and other potentially harmful components. Subconfluent cultures of Muller glia MIO-M1 cells were exposed to ATD (0.1 - 50 μg/mL) and cell viability, reactive oxygen species (ROS) production, antioxidant gene expression and transcriptomic analyses were performed. ATD exposure led to increased ROS without reducing viability, and was accompanied by reduced expression of antioxidant genes NRF2 and SOD1. Bulk RNA-seq analysis demonstrated downregulation of numerous mitochondrial genes and alterations in genes regulating migration, inflammation and adhesion. Therefore, these findings indicate that ATD pollution disrupts antioxidant protective mechanisms and mitochondrial gene expression in Muller glia, potentially leading to oxidative imbalance and transcriptional alterations that could contribute to retinal dysfunction.