Mechanistic study of silica nanoparticles on the size-dependent retinal toxicity in vitro and in vivo

BACKGROUND: Silica nanoparticles (SiO(2) NPs) are extensively applied in the biomedical field. The increasing medical application of SiO(2) NPs has raised concerns about their safety. However, studies on SiO(2) NP-induced retinal toxicity are lacking. METHODS: We investigated the retinal toxicity of SiO(2) NPs with different sizes (15 and 50 nm) in vitro and in vivo along with the underlying mechanisms. The cytotoxicity of SiO(2) NPs with different sizes was assessed in R28 human retinal precursor cells by determining the ATP content and LDH release. The cell morphologies and nanoparticle distributions in the cells were analyzed by phase-contrast microscopy and transmission electron microscopy, respectively. The mitochondrial membrane potential was examined by confocal laser scanning microscopy. The retinal toxicity induced by SiO(2) NPs in vivo was examined by immunohistochemical analysis. To further investigate the mechanism of retinal toxicity induced by SiO(2) NPs, reactive oxygen species (ROS) generation, glial cell activation and inflammation were monitored. RESULTS: The 15-nm SiO(2) NPs were found to have higher cytotoxicity than the larger NPs. Notably, the 15-nm SiO(2) NPs induced retinal toxicity in vivo, as demonstrated by increased cell death in the retina, TUNEL-stained retinal cells, retinal ganglion cell degeneration, glial cell activation, and inflammation. In addition, The SiO(2) NPs caused oxidative stress, as demonstrated by the increase in the ROS indicator H(2)DCF-DA. Furthermore, the pretreatment of R28 cells with N-acetylcysteine, an ROS scavenger, attenuated the ROS production and cytotoxicity induced by SiO(2) NPs. CONCLUSIONS: These results provide evidence that SiO(2) NPs induce size-dependent retinal toxicity and suggest that glial cell activation and ROS generation contribute to this toxicity. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01326-8.