Retinal cytotoxicity of silica and titanium dioxide nanoparticles

Abstract

The retina plays a key role in human vision. It is composed of cells that are essential for vision signal generation. Thus far, conventional medications have been ineffective for treating retinal diseases because of the intrinsic blood-retinal barrier. Nanoparticles (NPs) are promising effective platforms for ocular drug delivery. However, nanotoxicity in the retinal tissue has not received much attention. This study used R28 cells (a retinal precursor cell line that originated from rats) to investigate the safety of two commonly used types of NPs: silica nanoparticles (SiO₂NPs, 100 nm) and titanium dioxide nanoparticles (TiO₂NPs, 100 nm). Cellular viability and reactive oxygen species generation were measured after 24, 48, and 72 h of exposure to each NP. Cellular autophagy and the mTOR pathways were evaluated. The retinal toxicity of the NPs was investigated in vivo in rat models. Both types of NPs were found to induce significant dose-dependent toxicity on the R28 cells. A significant elevation of reactive oxygen species generation was also observed. Increased autophagy and decreased mTOR phosphorylation were observed after SiO₂NPs and TiO₂NPs exposure. The diffuse apoptosis of the retinal cellular layers was detected after intravitreal injection.

Keywords: cytotoxicity; nanoparticle; retina; silica nanoparticles; titanium dioxide.