Author:
Hao Shengjie,Chen Zhijian,Gu Yuzhou,Chen Lu,Sheng Feiyin,Xu Yili,Wu Di,Han Yu,Lu Bing,Chen Shuying,Zhao Wei,Yin Houfa,Wang Xiaofeng,Riazuddin S. Amer,Lou Xiaoming,Fu Qiuli,Yao Ke
Abstract
Abstract
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 further resulted in the circadian mismatches and dysfunction of LSPCs.
Conclusion
This study systematically demonstrates that PM2.5 impairs LSPCs and their microenvironment. Moreover, we show that circadian misalignment of LSPCs may be a new mechanism by which PM2.5 induces corneal diseases. Therapeutic options that target circadian rhythm may be viable options for improving LSPC functions and alleviating various PM2.5-associated corneal diseases.
Funder
the National Natural Science Foundation of China
National Natural Science Foundation of China
Zhejiang Province Key Research and Development Program
Fundamental Research Funds of the Central Universities
Publisher
Springer Science and Business Media LLC
Subject
Health, Toxicology and Mutagenesis,Toxicology,General Medicine
Cited by
1 articles.
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