Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou 510060, China; Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou 510060, China.
Biomed Pharmacother. 2019 Sep;117:109177. doi: 10.1016/j.biopha.2019.109177. Epub 2019 Jul 1.
Exposure to ambient fine particulate matter (fine PM) pollution has been previously associated with ocular surface diseases. But, to the best of our knowledge, the in vivo long-term effects of fine PM on the ocular surface have not been investigated. We aimed to evaluate the effects of fine PM on cultured human corneal epithelial (HCE) cells and on the ocular surfaces of mice, with standard reference material of fine PM(SRM 2786). We applied fine PM suspension to the eyes of C57BL/6 mice for up to 6 months. In vivo examinations, including tear secretion, tear film break-up time (TBUT) and corneal fluorescein staining, were performed in the 3 and 6 month. At the end of the in vivo study, the corneal histological changes and conjunctival goblet cells were examined by staining, and cytokines in tissue were also detected. In addition, HCE cells were treated with fine PM for 12 h and 24 h. Then, cell apoptosis and reactive oxygen species (ROS) formation was detected. We found that fine PM damages the mouse eye in a dose- and time-dependent manner. In mice, the tear secretion and tear film break-up time were significantly reduced, along with the development of corneal epithelial damage, apoptosis of conjunctival epithelial cells and hypoplasia of conjunctival goblet cells. In addition, IL-18, IL-22, IL-23 and MCP-1 were increased in both conjunctiva and cornea of the fine PM-treated animals. Furthermore, increased apoptosis and ROS production were observed in time- and dose-dependent manner in HCE cells after fine PM exposure for 12 h and 24 h. Our results indicate that fine PM is cytotoxic to both HCE cells and the ocular surface. Long-term topical application of fine PM suspension in mice results in ocular surface changes that are similar to those observed with dry eye.
暴露于环境细颗粒物（细 PM）污染以前与眼表面疾病相关。但是，据我们所知，细 PM 对眼表面的体内长期影响尚未得到研究。我们旨在评估细 PM 对培养的人角膜上皮（HCE）细胞和小鼠眼的影响，使用细 PM 的标准参考物质（SRM 2786）。我们将细 PM 混悬液应用于 C57BL/6 小鼠的眼睛长达 6 个月。在体内研究中，在第 3 个月和第 6 个月进行了包括泪液分泌、泪膜破裂时间（TBUT）和角膜荧光素染色在内的检查。在体内研究结束时，通过染色检查角膜组织学变化和结膜杯状细胞，并检测组织中的细胞因子。此外，还将 HCE 细胞用细 PM 处理 12 小时和 24 小时。然后，检测细胞凋亡和活性氧（ROS）形成。我们发现细 PM 以剂量和时间依赖性方式损害小鼠的眼睛。在小鼠中，泪液分泌和泪膜破裂时间明显减少，同时角膜上皮损伤、结膜上皮细胞凋亡和结膜杯状细胞发育不良。此外，在细 PM 处理的动物的结膜和角膜中，IL-18、IL-22、IL-23 和 MCP-1 均增加。此外，在 HCE 细胞中，细 PM 暴露 12 小时和 24 小时后，观察到细胞凋亡和 ROS 产生呈时间和剂量依赖性增加。我们的结果表明，细 PM 对 HCE 细胞和眼表面均具有细胞毒性。在小鼠中长期局部应用细 PM 混悬液可导致眼表面变化，类似于干燥眼观察到的变化。
