Titanium dioxide nanoparticles impair the inner blood-retinal barrier and retinal electrophysiology through rapid ADAM17 activation and claudin-5 degradation

BACKGROUND: Depending on their distinct properties, titanium dioxide nanoparticles (TiO(2)-NPs) are manufactured extensively and widely present in our daily necessities, with growing environmental release and public concerns. In sunscreen formulations, supplementation of TiO(2)-NPs may reach up to 25% (w/w). Ocular contact with TiO(2)-NPs may occur accidentally in certain cases, allowing undesirable risks to human vision. This study aimed to understand the barrier integrity of retinal endothelial cells in response to TiO(2)-NP exposure. bEnd.3 cells and human retinal endothelial cells (HRECs) were exposed to TiO(2)-NP, followed by examination of their tight junction components and functions. RESULTS: TiO2-NP treatment apparently induced a broken structure of the junctional plaques, conferring decreased transendothelial electrical resistance, a permeable paracellular cleft, and improved cell migration in vitro. This might involve rapid activation of metalloproteinase, a disintegrin and metalloproteinase 17 (ADAM17), and ADAM17-mediated claudin-5 degradation. For the in vivo study, C57BL/6 mice were administered a single dose of TiO2-NP intravitreally and then subjected to a complete ophthalmology examination. Fluorescein leakage and reduced blood flow at the optical disc indicated a damaged inner blood-retinal barrier induced by TiO(2)-NPs. Inappreciable change in the thickness of retinal sublayers and alleviated electroretinography amplitude were observed in the TiO(2)-NP-treated eyes. CONCLUSIONS: Overall, our data demonstrate that TiO2-NP can damage endothelial cell function, thereby affecting retinal electrophysiology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12989-020-00395-7.