Diesel particulate matter2.5 promotes epithelial-mesenchymal transition of human retinal pigment epithelial cells via generation of reactive oxygen species.

Although several studies have linked PM2.5 (particulate matter with a diameter less than 2.5 μm) to ocular surface diseases such as keratitis and conjunctivitis, very few studies have previously addressed its effect on the retina. Therefore, the aim of this study was to evaluate the effect of PM2.5 on epithelial-mesenchymal transition (EMT), a process involved in disorders of the retinal pigment epithelial (RPE) on APRE-19 cells. PM2.5 changed the phenotype of RPE cells from epithelial to fibroblast-like mesenchymal, and increased cell migration. Exposure to PM2.5 markedly increased the expression of mesenchymal markers, but reduced the levels of epithelial markers. Moreover, PM2.5 promoted the phosphorylation of MAPKs and the expression of transforming growth factor-β (TGF-β)-mediated nuclear transcriptional factors. However, these PM2.5-mediated changes were completely reversed by LY2109761, a small molecule inhibitor of the TGF-β receptor type I/II kinases, and N-acetyl-L-cysteine (NAC), a reactive oxygen species (ROS) scavenger. Interestingly, NAC, but not LY2109761, effectively restored the PM2.5-induced mitochondrial defects, including increased ROS, decreased mitochondrial activity, and mitochondrial membrane potential disruption. Collectively, our findings indicate that the TGF-β/Smad/ERK/p38 MAPK signaling pathway is activated downstream of cellular ROS during PM2.5-induced EMT. The present study provides the first evidence that EMT of RPE may be one of the mechanisms of PM2.5-induced retinal dysfunction.