Silica nanoparticles, which are potential drug carriers for glaucoma treatment, may induce mild dose-dependent cytotoxicity but not so severe as to compromise a mammalian target of rapamycin pathway in immortalized trabecular meshwork cells.
Nanoparticle-based ophthalmic drug delivery is a promising field of drug development. In this study, we evaluated the effect of nonporous silica nanoparticles (SiNPs) on human trabecular meshwork (TM) cells.
TM cells were exposed to different concentrations (0 to 100▒µg/mL) of SiNPs (50, 100, and 150▒nm) for up to 48 hours. Transmission electron microscopy (TEM) confirmed the intracellular distribution of SiNPs. Cellular viability assay, reactive oxygen species (ROS) generation, autophagy, and activation of the mammalian target of rapamycin (mTOR) pathway were evaluated. Histologic analysis of the TM structure was performed after intracameral injection of SiNPs (0.05▒mL of 200▒µg/mL concentration) in rabbits.
SiNPs were taken up by TM cells and localized in the cytoplasm. Neither nuclear entry nor mitochondrial damage was observed. SiNPs induced a mild but dose-dependent increase of lactate dehydrogenase. However, neither increase of intracellular ROS levels nor apoptosis was observed after SiNPs exposure. Significant co-activation of autophagy and the mTOR pathway was observed with exposure to SiNPs. Aqueous plexus structure was well maintained without inflammation in rabbits after SiNPs exposure.
SiNPs induce mild and dose-dependent cytotoxicity in TM cells. However, the toxicity level is not enough to compromise the mTOR pathway of TM cells and histologic structure of the aqueous plexus tissue.