PMID- 33086260 OWN - NLM STAT- MEDLINE DCOM- 20210903 LR - 20210903 IS - 1536-481X (Electronic) IS - 1057-0829 (Linking) VI - 30 IP - 2 DP - 2021 Feb 1 TI - Effects of Nonporous Silica Nanoparticles on Human Trabecular Meshwork Cells. PG - 195-202 LID - 10.1097/IJG.0000000000001709 [doi] AB - PRECIS: Silica nanoparticles (SiNPs), 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 (mTOR) pathway in immortalized trabecular meshwork (TM) cells. PURPOSE: Nanoparticle-based ophthalmic drug delivery is a promising field of drug development. In this study, we evaluated the effect of nonporous SiNPs on human TM cells. METHODS: TM cells were exposed to different concentrations (0 to 100 microg/mL) of SiNPs (50, 100, and 150 nm) for up to 48 hours. Transmission electron microscopy confirmed the intracellular distribution of SiNPs. Cellular viability assay, reactive oxygen species generation, autophagy, and activation of the mTOR pathway were evaluated. Histologic analysis of the TM structure was performed after intracameral injection of SiNPs (0.05 mL of 200 microg/mL concentration) in rabbits. RESULTS: 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 reactive oxygen species levels nor apoptosis was observed after SiNPs exposure. Significant coactivation of autophagy and the mTOR pathway were observed with exposure to SiNPs. Aqueous plexus structure was well maintained without inflammation in rabbits after SiNPs exposure. CONCLUSIONS: 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. CI - Copyright (c) 2020 Wolters Kluwer Health, Inc. All rights reserved. FAU - Kim, Martha AU - Kim M AD - Department of Ophthalmology, Dongguk University Ilsan Hospital, Goyang. FAU - Park, Joo-Hee AU - Park JH AD - Department of Ophthalmology, Dongguk University Ilsan Hospital, Goyang. AD - Department of Biochemistry, College of Medicine, Dongguk University, Gyeongju. FAU - Jeong, Hyejoong AU - Jeong H AD - Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, South Korea. FAU - Hong, Jinkee AU - Hong J AD - Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, South Korea. FAU - Park, Choul Yong AU - Park CY AD - Department of Ophthalmology, Dongguk University Ilsan Hospital, Goyang. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Glaucoma JT - Journal of glaucoma JID - 9300903 RN - 7631-86-9 (Silicon Dioxide) SB - IM MH - Animals MH - Cell Survival MH - Humans MH - Intraocular Pressure MH - *Nanoparticles/toxicity MH - Rabbits MH - *Silicon Dioxide/toxicity MH - Trabecular Meshwork COIS- Disclosure: The authors declare no conflict of interest. EDAT- 2020/10/22 06:00 MHDA- 2021/09/04 06:00 CRDT- 2020/10/21 20:08 PHST- 2020/03/30 00:00 [received] PHST- 2020/09/29 00:00 [accepted] PHST- 2020/10/22 06:00 [pubmed] PHST- 2021/09/04 06:00 [medline] PHST- 2020/10/21 20:08 [entrez] AID - 00061198-202102000-00014 [pii] AID - 10.1097/IJG.0000000000001709 [doi] PST - ppublish SO - J Glaucoma. 2021 Feb 1;30(2):195-202. doi: 10.1097/IJG.0000000000001709.