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

Autor: Zhuhong Zhang, Laien Zhao, Yuanyuan Ma, Jia Liu, Yanmei Huang, Xiaoxuan Fu, Shengjun Peng, Xiaojie Wang, Yun Yang, Xiaoyan Zhang, Wanru Ding, Jinguo Yu, Yanping Zhu, Hua Yan, Shubin Yang
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Nanobiotechnology, Vol 20, Iss 1, Pp 1-19 (2022)
Druh dokumentu: article
ISSN: 1477-3155
DOI: 10.1186/s12951-022-01326-8
Popis: Abstract Background Silica nanoparticles (SiO2 NPs) are extensively applied in the biomedical field. The increasing medical application of SiO2 NPs has raised concerns about their safety. However, studies on SiO2 NP-induced retinal toxicity are lacking. Methods We investigated the retinal toxicity of SiO2 NPs with different sizes (15 and 50 nm) in vitro and in vivo along with the underlying mechanisms. The cytotoxicity of SiO2 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 SiO2 NPs in vivo was examined by immunohistochemical analysis. To further investigate the mechanism of retinal toxicity induced by SiO2 NPs, reactive oxygen species (ROS) generation, glial cell activation and inflammation were monitored. Results The 15-nm SiO2 NPs were found to have higher cytotoxicity than the larger NPs. Notably, the 15-nm SiO2 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 SiO2 NPs caused oxidative stress, as demonstrated by the increase in the ROS indicator H2DCF-DA. Furthermore, the pretreatment of R28 cells with N-acetylcysteine, an ROS scavenger, attenuated the ROS production and cytotoxicity induced by SiO2 NPs. Conclusions These results provide evidence that SiO2 NPs induce size-dependent retinal toxicity and suggest that glial cell activation and ROS generation contribute to this toxicity. Graphical Abstract
Databáze: Directory of Open Access Journals
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