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Martha Kim, Choul Yong Park; The Effects of Nonporous Silica Nanoparticles on Human Trabecular Meshwork Cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4717.
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© ARVO (1962-2015); The Authors (2016-present)
Silica nanoparticles (SiNPs) are a promising drug-carrier in glaucoma treatment. Before introducing the SiNPs as a drug-carrier, the toxicity evaluation of SiNPs on ocular tissues is essential. We evaluated the effect of various sizes of nonporous SiNPs on human trabecular meshwork (TM) cells.
Three different sizes of SiNPs (50, 100, and 150 nm) were manufactured. The immortalized human primary TM cells were exposed to different concentrations (0, 10, 25, 50, 100 µg/ml) of SiNPs for up to 48 hours. Cellular viability, lactate dehydrogenase (LDH) assay, intracellular reactive oxygen species (ROS) generation, autophagy and mammalian target of rapamycin (mTOR) pathway activation were evaluated. Intracellular distribution of SiNPs was evaluated with transmission electron microscopy (TEM). In vivo rabbit TM cell toxicity assay was performed by intracemeral injection of SiNP solution (0.05 ml) of each size of SiNPs (200 μg/mL).
The SiNPs did not affect viability and LDH levels significantly. Each three size of SiNPs increased intracellular ROS levels of TM cells dose dependently, however there was no statistical significance. TEM revealed that SiNPs were localized mainly in cytoplasm around the nucleus within autophagic vacuoles. Autophagy showed significant activation and phosphorylated mTOR increased with 50, 100 and 150 nm SiNPs. The histopathologic structure of TM tissue was well maintained, and no significant difference was found in treated rabbit eyes.
The SiNPs did not induce significant cytotoxicity in TM cells at concentrations up to 100 µg/ml. In vivo study, TM tissue showed no abnormality in morphologic and histopathologic assay. The SiNPs could be promising drug-carriers for glaucoma treatment.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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