Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong.
Lam Kin Chung. Jet King-Shing Ho Glaucoma Treatment and Research Centre, The Chinese University of Hong Kong, Hong Kong.
Oxid Med Cell Longev. 2022 Nov 10;2022:7435754. doi: 10.1155/2022/7435754. eCollection 2022.
Primary open-angle glaucoma (POAG) is the most common form of glaucoma, for which elevated intraocular pressure (IOP) is a major risk factor. IOP is mainly regulated by dynamic balance of aqueous humor (AH) production and outflow via the conventional trabecular meshwork/Schlemm's canal (TM/SC) pathway. Dysfunctions of TM cells due to endoplasmic reticulum (ER) stress have been demonstrated to increase the resistance of AH outflow, resulting in IOP elevation. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic component in green tea, has been shown to alleviate ER stress in several diseases while its potential roles in alleviating ER stress in TM cells have not been determined. In this study, we investigate the mitigation of tunicamycin-induced ER stress in TM cells by EGCG. MTT assay was used to measure the cell viability of human TM (HTM) cells and primary porcine TM (PTM) cells. ER stress levels in both HTM cells and primary PTM cells were detected by quantitative real-time PCR. The primary PTM cells isolated from porcine TM tissues were characterized by immunostaining. We found that 40 M and 80 M EGCG pretreatment substantially promoted HTM cell survival under 3 M tunicamycin-induced ER stress. Pretreatment of 40 M EGCG markedly reduced the expression of ER stress markers , , and evoked by 3 M tunicamycin in HTM cells. Furthermore, 40 M EGCG pretreatment significantly decreased the expressions of , , and at the mRNA level induced by 3 M tunicamycin and improved cell viability in primary PTM cells. Our results show that EGCG is capable of protecting TM cells from ER stress. EGCG provides a promising therapeutic option for POAG treatment.
原发性开角型青光眼（POAG）是最常见的青光眼类型，眼内压（IOP）升高是其主要危险因素。IOP 主要通过房水（AH）的产生和通过传统小梁网/施莱姆管（TM/SC）途径流出的动态平衡来调节。内质网（ER）应激导致 TM 细胞功能障碍已被证明会增加 AH 流出阻力，导致 IOP 升高。表没食子儿茶素没食子酸酯（EGCG）是绿茶中含量最丰富的多酚成分，已被证明可减轻几种疾病中的 ER 应激，但其在减轻 TM 细胞 ER 应激中的潜在作用尚未确定。在这项研究中，我们研究了 EGCG 减轻 TM 细胞中衣霉素诱导的 ER 应激的作用。MTT 测定法用于测量人 TM（HTM）细胞和原代猪 TM（PTM）细胞的细胞活力。通过实时定量 PCR 检测 HTM 细胞和原代 PTM 细胞中的 ER 应激水平。通过免疫染色对从猪 TM 组织中分离的原代 PTM 细胞进行了特征描述。我们发现，40μM 和 80μM EGCG 预处理可显著促进 HTM 细胞在 3μM 衣霉素诱导的 ER 应激下的存活。40μM EGCG 预处理可显著降低 HTM 细胞中 3μM 衣霉素诱导的 ER 应激标志物 、 和 的表达。此外，40μM EGCG 预处理可显著降低 3μM 衣霉素诱导的 HTM 细胞中 、 和 的表达，并改善原代 PTM 细胞的细胞活力。我们的结果表明，EGCG 能够保护 TM 细胞免受 ER 应激。EGCG 为 POAG 的治疗提供了有前景的治疗选择。
