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Deoxynivalenol Damages Corneal Epithelial Cells and Exacerbates Inflammatory Response in Fungal Keratitis

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Abstract

Background

Fungal keratitis (FK) is a kind of infectious keratopathy with a high rate of blindness worldwide. Deoxynivalenol (DON) has been proven to have multiple toxic effects on humans and animals.

Objectives

The aim of this study was to explore a possible pathogenic role of DON in FK.

Methods

We first made an animal model of FK in New Zealand white rabbits, and then attempted to detect DON in a culture medium in which Fusarium solani had been grown and also in the corneal tissue of the animal model of Fusarium solani keratitis. Next, a model of DON damage in human corneal epithelial cells (HCECs) was constructed to evaluate effects of DON on the activity, migration ability, cell cycle, and apoptosis in the HCECs. Then, putative the toxic damaging effects of DON on rabbit corneal epithelial cells and the impact of the repair cycle were studied. The expression levels of inflammatory factors in the corneas of the animal model and in the model of DON-damaged HCECs were measured.

Results

The Fusarium solani strain used in this study appeared to have the potential to produce DON, since DON was detected in the corneal tissue of rabbits which had been inoculated with this Fusarium solani strain. DON was found to alter the morphology of HCECs, to reduce the activity and to inhibit the proliferation and migration of HCECs. DON also induced the apoptosis and S-phase arrest of HCECs. In addition, DON was found to damage rabbit corneal epithelial cells, to prolong the corneal epithelial regeneration cycle, and to be associated with the upregulated expression of inflammatory factors in HCECs and rabbit corneas.

Conclusions

DON appears to have a toxic damaging effect on HCECs in FK, and to induce the expression of inflammatory factors, leading to the exacerbation of keratitis and the formation of new blood vessels. Future studies will explore the possibility of developing a test to detect DON in ophthalmic settings to aid the rapid diagnosis of FK, and to develop DON neutralizers and adsorbents which have the potential to improve keratocyte status, inhibit apoptosis, and alleviate inflammation, therein providing new thinking for therapy of clinical FK.

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Funding

This research was funded by National Natural Science Foundation of China, Grant number: 81970806, 82271094 and Science and Technology Projects in Guangzhou, Grant number: 202201020030, 202201020015.

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Authors and Affiliations

  1. Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Qi Shi, QingQing Li, Changlin Wu, Shisi Ma, Chunlan Liang, Jingxiang Zhong & Lian Liu

  2. Department of Clinical Laboratory, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Xiaoyi Fan

  3. Department of Ophthalmology, The Sixth Affiliated Hospital, Jinan University, Dongguan, 523000, China

    Jingxiang Zhong

  4. Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, 515282, China

    Shisi Ma

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  1. Qi Shi
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Contributions

All authors contributed to the study conception and design. Material preparation, experimentation and analysis were performed by QS, QL, SM, CW, CL, and XF. The first draft of the manuscript was written by QS. The manuscript was reviewed and edited by SM, JZ and LL. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jingxiang Zhong or Lian Liu.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical Approval

The animal study protocol was approved by the Laboratory Animal Ethics Committee of Jinan University (protocol code No. IACUC-20210324-01) for studies involving animals.

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Shi, Q., Li, Q., Wu, C. et al. Deoxynivalenol Damages Corneal Epithelial Cells and Exacerbates Inflammatory Response in Fungal Keratitis. Mycopathologia 189, 28 (2024). https://doi.org/10.1007/s11046-024-00829-2

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