Department of Ophthalmology and Visual Sciences, Hong Kong Eye Hospital, The Chinese University of Hong Kong, 147K Argyle Street, Kowloon, Hong Kong.
Department of Ophthalmology, The Fourth People's Hospital of Shenyang, Key Laboratory of Ophthalmology of Shenyang, Shenyang Eye Research Institute, Shenyang, China.
Mol Neurobiol. 2019 Sep;56(9):6586-6593. doi: 10.1007/s12035-019-1559-5. Epub 2019 Mar 22.
Glaucoma is a chronic optic neuropathy that could lead to permanent vision loss. Primary open-angle glaucoma (POAG) is the most common type of glaucoma, with elevated intraocular pressure (IOP) as a major risk factor. IOP is mainly regulated by trabecular meshwork (TM), an important component of the conventional aqueous humor (AH) outflow pathway. TM cells are constantly subjected to oxidative stress. Long-term exposure to oxidative stress has been shown to cause elevation of AH outflow resistance, leading to higher IOP. In this study, we induced chronic oxidative stress in human trabecular meshwork (TM-1) cells with 1 μM rotenone and investigated the levels of reactive oxygen species (ROS), autophagy, and mitochondrial functions. Protective effects of rapamycin, an inducer of autophagy, were also investigated. Our data indicated that rotenone significantly increased oxidative stress, but not autophagy, in TM-1 cells. Rapamycin at 10 nM effectively suppressed the rotenone-induced cell apoptosis, as well as the ROS elevation. The protective effects of rapamycin could be associated to the induction of autophagy and removal of damaged mitochondria in TM-1 cells. Our results suggest autophagy has important roles in protecting TM-1 cells from oxidative stress, which could be further developed into a novel treatment to POAG.
青光眼是一种慢性视神经病变，可导致永久性视力丧失。原发性开角型青光眼（POAG）是最常见的青光眼类型，眼内压（IOP）升高是主要危险因素。IOP 主要由小梁网（TM）调节，TM 是传统房水（AH）流出途径的重要组成部分。TM 细胞不断受到氧化应激的影响。长期暴露于氧化应激已被证明会导致 AH 流出阻力增加，从而导致 IOP 升高。在这项研究中，我们用 1μM 鱼藤酮诱导人小梁网（TM-1）细胞发生慢性氧化应激，并研究了活性氧（ROS）、自噬和线粒体功能的水平。还研究了自噬诱导剂雷帕霉素的保护作用。我们的数据表明，鱼藤酮显著增加了 TM-1 细胞的氧化应激，但没有增加自噬。10 nM 的雷帕霉素有效地抑制了鱼藤酮诱导的细胞凋亡以及 ROS 的升高。雷帕霉素的保护作用可能与 TM-1 细胞中自噬的诱导和受损线粒体的清除有关。我们的结果表明，自噬在保护 TM-1 细胞免受氧化应激方面起着重要作用，这可能进一步开发为治疗 POAG 的新方法。
