Long-term PM2.5 exposure disrupts corneal epithelial homeostasis by impairing limbal stem/progenitor cells in humans and rat models

作者：Shengjie Hao, Zhijian Chen, Yuzhou Gu, Lü Chen, Feiyin Sheng, Yili Xu, Di Wu, Yu Han, Bing Lu, Shuying Chen, Wei Zhao, Houfa Yin, Xiaofeng Wang, Sheikh Riazuddin, Xiaoming Lou, Qiuli Fu, Ke Yao · 发表于：Particle and Fibre Toxicology · 年份：2023 · DOI：10.1186/s12989-023-00540-y · 被引用次数：29 · 研究领域：Corneal Surgery and Treatments、Corneal surgery and disorders、Ocular Surface and Contact Lens

BACKGROUND: Limbal stem/progenitor cells (LSPCs) play a crucial role in maintaining corneal health by regulating epithelial homeostasis. Although PM2.5 is associated with the occurrence of several corneal diseases, its effects on LSPCs are not clearly understood. METHODS: In this study, we explored the correlation between PM2.5 exposure and human limbal epithelial thickness measured by Fourier-domain Optical Coherence Tomography in the ophthalmologic clinic. Long- and short-term PM2.5 exposed-rat models were established to investigate the changes in LSPCs and the associated mechanisms. RESULTS: We found that people living in regions with higher PM2.5 concentrations had thinner limbal epithelium, indicating the loss of LSPCs. In rat models, long-term PM2.5 exposure impairs LSPCs renewal and differentiation, manifesting as corneal epithelial defects and thinner epithelium in the cornea and limbus. However, LSPCs were activated in short-term PM2.5-exposed rat models. RNA sequencing implied that the circadian rhythm in LSPCs was perturbed during PM2.5 exposure. The mRNA level of circadian genes including Per1, Per2, Per3, and Rev-erbα was upregulated in both short- and long-term models, suggesting circadian rhythm was involved in the activation and dysregulation of LSPCs at different stages. PM2.5 also disturbed the limbal microenvironment as evidenced by changes in corneal subbasal nerve fiber density, vascular density and permeability, and immune cell infiltration, which furthe...