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Airborne particulate matter (PM2.5) triggers ocular hypertension and glaucoma through pyroptosis
Particle and Fibre Toxicology ( IF 10 ) Pub Date : 2021-03-04 , DOI: 10.1186/s12989-021-00403-4
Liping Li 1 , Chao Xing 2 , Ji Zhou 3 , Liangliang Niu 1 , Bin Luo 4, 5 , Maomao Song 1 , Jingping Niu 4 , Ye Ruan 4 , Xinghuai Sun 1, 6, 7 , Yuan Lei 1, 6
Affiliation  

Particulate matter (PM) is strongly linked to human health and has detrimental effects on the eye. Studies have, however, focused on the ocular surface, with limited research on the impact of PM2.5 on intraocular pressure (IOP). To investigate the impact of PM2.5 on IOP and the associated mechanism, C57BL/6 mouse eyes were topically exposed to a PM2.5 suspension for 3 months, and human trabecular meshwork (HTM) cells were subjected to various PM2.5 concentrations in vitro. Cell viability, NLRP3/caspase-1, IL-1β, and GSDMD expression, reactive oxygen species (ROS) production and cell contractility were measured by western blot, ELISA, cell counting kit-8, ROS assay kit or a cell contractility assay. ROS scavenger N-acetyl-L-cysteine (NAC) and caspase-1 inhibitor VX-765 were used to intervene in PM2.5-induced damages. The results revealed that the IOP increased gradually after PM2.5 exposure, and upregulations of the NLRP3 inflammasome, caspase-1, IL-1β, and GSDMD protein levels were observed in outflow tissues. PM2.5 exposure decreased HTM cell viability and affected contraction. Furthermore, elevated ROS levels were observed as well as an activation of the NLRP3 inflammasome and downstream inflammatory factors caspase-1 and IL-1β. NAC improved HTM cell viability, inhibited the activation of the NLRP3 inflammasome axis, and HTM cell contraction by scavenging ROS. VX-765 showed similar protection against the PM2.5 induced adverse effects. This study provides novel evidence that PM2.5 has a direct toxic effect on intraocular tissues and may contribute to the initiation and development of ocular hypertension and glaucoma. This occurs as a result of increased oxidative stress and the subsequent induction of NLRP3 inflammasome mediated pyroptosis in trabecular meshwork cells.

中文翻译:

空气中的颗粒物 (PM2.5) 通过焦亡引发高眼压症和青光眼

颗粒物 (PM) 与人类健康密切相关,对眼睛有不利影响。然而,研究集中在眼表,对 PM2.5 对眼内压 (IOP) 的影响的研究有限。为了研究 PM2.5 对 IOP 的影响和相关机制,C57BL/6 小鼠眼睛局部暴露于 PM2.5 悬浮液中 3 个月,并且人小梁网 (HTM) 细胞在不同浓度的 PM2.5体外。细胞活力、NLRP3/caspase-1、IL-1β 和 GSDMD 表达、活性氧 (ROS) 产生和细胞收缩性通过蛋白质印迹、ELISA、细胞计数试剂盒 8、ROS 测定试剂盒或细胞收缩性测定来测量。ROS 清除剂 N-乙酰-L-半胱氨酸 (NAC) 和 caspase-1 抑制剂 VX-765 用于干预 PM2.5 引起的损伤。结果表明,暴露于 PM2.5 后眼压逐渐升高,流出组织中观察到 NLRP3 炎症小体、caspase-1、IL-1β 和 GSDMD 蛋白水平上调。PM2.5 暴露会降低 HTM 细胞的活力并影响收缩。此外,观察到 ROS 水平升高以及 NLRP3 炎症小体和下游炎症因子 caspase-1 和 IL-1β 的激活。NAC 通过清除 ROS 提高了 HTM 细胞活力,抑制了 NLRP3 炎性体轴的激活和 HTM 细胞收缩。VX-765 对 PM2.5 引起的不利影响表现出类似的保护作用。这项研究提供了新的证据,证明 PM2.5 对眼内组织有直接的毒性作用,并可能导致高眼压症和青光眼的发生和发展。
更新日期:2021-03-04
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