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Electroacupuncture regulates the P2X7R-NLRP3 inflammatory cascade to relieve decreased sensation on ocular surface of type 2 diabetic rats with dry eye

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Abstract

Dry eye (DE) is a prevalent ocular surface disease in patients with type 2 diabetes (T2DM). However, current medications are ineffective against decreased sensation on the ocular surface. While electroacupuncture (EA) effectively alleviates decreased sensation on ocular surface of DE in patients with T2DM, the neuroprotective mechanism remains unclear. This study explored the pathogenesis and therapeutic targets of T2DM-associated DE through bioinformatics analysis. It further investigated the underlying mechanism by which EA improves decreased sensation on the ocular surface of DE in rats with T2DM. Bioinformatic analysis was applied to annotate the potential pathogenesis of T2DM DE. T2DM and DE was induced in male rats. Following treatment with EA and fluorometholone, comprehensive metrics were assessed. Additionally, the expression patterns of key markers were studied. Key targets such as NLRP3, Caspase-1, and NOD-like receptor signaling may be involved in the pathogenesis of T2DM DE. EA treatment improved ocular measures. Furthermore, EA potently downregulated P2X7R, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 expression within the trigeminal ganglion and spinal trigeminal nucleus caudalis. Targeted P2X7R antagonist (A-438079) and agonist (BzATP) employed as controls to decipher the biochemistry of the therapeutic effects of EA showed an anti-inflammatory effect with A-438079, while BzATP blocked the anti-inflammatory effect of EA. EA relieved DE symptoms and attenuated inflammatory damage to sensory nerve pathways in T2DM rats with DE. These findings suggest a crucial role of EA inhibition of the P2X7R-NLRP3 inflammatory cascade to provide these benefits.

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The data used to support the results of this study can be obtained from the corresponding author upon reasonable request. All the images are consented to be published.

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Acknowledgements

We would like to extend our gratitude to Dr. Qin-Mei Sun and Zhuo-Yuan Wang from the Shanghai University of Traditional Chinese Medicine for their invaluable suggestions on data processing and manuscript composition.

Funding

This study was supported by the National Natural Science Foundation of China (No. 82074526; Nanjing, China) and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (No. KYCX23_2138; Nanjing, China).

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Author notes

  1. Mi-Mi Wan and Zhang-Yitian Fu contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. Department of Ophthalmology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China

    Mi-Mi Wan, Zhang-Yitian Fu & Wei-Ping Gao

  2. Department of Ophthalmology, Kunshan Hospital of Chinese Medicine, Suzhou, China

    Tuo Jin

  3. Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China

    Zhuo-Yuan Wang

  4. Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China

    Xin-Yi Sun

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  1. Mi-Mi Wan
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Contributions

WPG and XYS conceptualized and designed the experiments. ZYTF and MMW executed the animal experiments. ZYW completed the data mining for bioinformatics analysis. TJ and ZYTF performed the statistical analyses, while TJ and MMW interpreted the data. MMW wrote the initial draft of the manuscript. All authors approved the final version of the manuscript.

Corresponding authors

Correspondence to Xin-Yi Sun or Wei-Ping Gao.

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The animal experiments conformed to the relevant provisions of the national experimental animal welfare ethics and were approved by the Ethics Committee of the Affiliated Hospital of Nanjing University of Chinese Medicine (batch number: 2022NL-KS093).

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Wan, MM., Fu, ZY., Jin, T. et al. Electroacupuncture regulates the P2X7R-NLRP3 inflammatory cascade to relieve decreased sensation on ocular surface of type 2 diabetic rats with dry eye. Purinergic Signalling (2024). https://doi.org/10.1007/s11302-024-09991-0

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