Department of Ophthalmology, Dongguk University Ilsan Hospital, Goyang.
Department of Biochemistry, College of Medicine, Dongguk University, Gyeongju.
J Glaucoma. 2021 Feb 1;30(2):195-202. doi: 10.1097/IJG.0000000000001709.
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.
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.
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 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 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 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.
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.
作为治疗青光眼的潜在药物载体，硅纳米颗粒（SiNPs）可能会引起轻微的剂量依赖性细胞毒性，但不会严重影响永生化小梁网（TM）细胞中的哺乳动物雷帕霉素靶蛋白（mTOR）通路。
基于纳米颗粒的眼科药物输送是药物开发的一个有前途的领域。在这项研究中，我们评估了非多孔 SiNPs 对人 TM 细胞的影响。
TM 细胞暴露于不同浓度（0 至 100μg/ml）的 SiNPs（50、100 和 150nm）中，时间长达 48 小时。透射电子显微镜证实了 SiNPs 的细胞内分布。评估细胞活力测定、活性氧生成、自噬和 mTOR 通路的激活。在兔眼内注射 SiNPs（0.05ml 浓度为 200μg/ml）后，对 TM 结构进行组织学分析。
SiNPs 被 TM 细胞摄取并定位于细胞质中。未观察到核内进入或线粒体损伤。SiNPs 诱导了轻微但剂量依赖性的乳酸脱氢酶增加。然而，在 SiNPs 暴露后，未观察到细胞内活性氧水平增加或凋亡。暴露于 SiNPs 后，观察到自噬和 mTOR 通路的显著共激活。在 SiNPs 暴露后，兔眼房水中的结构得到了很好的维持，没有炎症。
SiNPs 在 TM 细胞中引起轻微的、剂量依赖性的细胞毒性。然而，毒性水平不足以损害 TM 细胞的 mTOR 通路和房水组织的组织学结构。
