Toxic effect of titanium dioxide nanoparticles on corneas in vitro and in vivo

Titanium dioxide nanoparticles (TiO(2) NPs) are widely used in a variety of areas. However, TiO(2) NPs possess cytotoxicity which involves oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key molecule preventing cells from oxidative stress damage. In the current study, we explored the effect of Nrf2 signaling pathway in TiO(2) NPs-induced corneal endothelial cell injury. Firstly, we found TiO(2) NPs inhibited proliferation and damaged morphology and mitochondria of mouse primary corneal endothelial cells. Moreover, TiO(2) NPs-induced oxidative damage of mouse primary corneal endothelial cells was inhibited by antioxidant NAC by evaluating production of reactive oxygen species (ROS), malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Next, flow cytometry analysis showed TiO(2) NPs promoted apoptosis and cell cycle G2/M phase arrest of mouse primary corneal endothelial cells. Further investigation suggested that Nrf2 signaling pathway activation and the downregulation of ZO-1, β-catenin and Na-K-ATPase were involved in TiO(2) NPs-induced mouse primary corneal endothelial cell injury. Our research highlighted the toxic effect of TiO(2) NPs on corneas in vitro and in vivo, providing an alternative insight into TiO(2) NPs-induced corneal endothelial cell injury.