BMSC Alleviates Dry Eye by Inhibiting the ROS-NLRP3-IL-1β Signaling Axis by Reducing Inflammation Levels

Abstract

Purpose

Bone marrow mesenchymal stem cells (BMSC) have multiple biological functions and are widely involved in regulating inflammatory diseases, tissue repair and regeneration. However, the mechanism of their action in dry eye disease (DED) is currently unclear. The purpose of this study was to investigate the effect of BMSCs in the treatment of dry eye mice and to explore its specific therapeutic mechanism.

Methods

Mouse corneal epithelial cells (MCECs) were treated with 500 mOsM sodium chloride hypertonic solution to induce a DED cell model. The dry eye animal model was constructed by adding 5 μL 0.2% benzalkonium chloride solution to mouse eyes. Western blotting was used to detect the expression of related proteins, and flow cytometry, enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, hematoxylin-eosin (HE) staining, and periodic acid schiff (PAS) staining were used to detect cell and eye tissue damage.

Results

The experimental results showed that BMSCs can reduce the levels of reactive oxygen species (ROS) and inflammatory factors in MCECs, promote cell proliferation, inhibit cell apoptosis, improve the integrity of the corneal epithelial layer in vivo, promote an increase in the number of goblet cells, and alleviate DED. Further exploration of the molecular mechanism of BMSCs treatment revealed that BMSCs alleviate the progression of DED by inhibiting the ROS-NLRP3-IL-1β signaling pathway.

Conclusion

BMSCs inhibit ROS-NLRP3-IL-1β signaling axis, reducing inflammation levels and alleviating dry eye symptoms. These findings provide new ideas and a basis for the treatment of DED and provide an experimental basis for further research on the application value of BMSCs in alleviating DED.

Keywords:

• Dry eye disease
• bone marrow mesenchymal stem cells
• ROS-NLRP3-IL-1β signaling pathway
• inflammatory response
• reactive oxygen species

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval and consent to participate

All animal experimental protocols were approved by the Experimental Animal Ethics Committee of Kunming Yan’an Hospital (2021070). All methods are performed in accordance with the relevant guidelines and regulations and in accordance with ARRIVE guidelines.

Authors’ contributions

All authors contributed substantially to this manuscript. Hongxia Zhao and Yang He performed the majority of experiments and data analysis. Dandan Zhao contributed to carrying out the experiments and interpreted the results. Dandan Zhao wrote the manuscript. Meixia Zhang contributed to the conception and designed this study and guided the writing of the manuscript. All authors read and approved the final manuscript.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by the Health Research Project of Kunming Health Commission [2020-07-02-112], Yunnan Provincial Basic Research Program [202301AY070001-156], National Natural Science Foundation of China [82360201], and Yunnan Province Young and Middle-aged Academic and Technical Leaders Reserve Talent Project [02405AC350103].