- 作者: Hsiao-Hsuan Wang, Wei-Yu Chen, Yi-Hsun Huang, Sheng-Min Hsu, Yeou-Ping Tsao, Yu-Hsiang Hsu & Ming-Shi Chang
- 作者服務機構: 1.Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 2.Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan 3.Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan 4.Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan 5.Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan 6.Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan 7.Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
- 中文摘要:
- 英文摘要:
Background: Dry eye disease (DED) is a common disease in ophthalmology, afecting millions of people worldwide.
Recent studies have shown that infammation is the core mechanism of DED. IL-20 is a proinfammatory cytokine
involved in various infammatory diseases. Therefore, we aimed to explore the role of this cytokine in the pathogen‑
esis of DED and evaluate the therapeutic potential of the anti-IL-20 monoclonal antibody (mAb) 7E for DED treatment.
Methods: Clinical tear samples from patients with DED and non-DED controls were collected and their IL-20 protein
levels were determined. We established three DED animal models to explore the role of IL-20 and the efcacy of IL-20
antibody in DED. Benzalkonium chloride (BAC)-induced over-evaporative DED, extra-orbital lacrimal gland excision
(LGE)-induced aqueous tear-defcient DED, and desiccating stress (DS)-induced combined over-evaporative and
aqueous tear-defcient DED animal models were established to investigate the role of IL-20. The anti-IL-20 antibody
7E was established to neutralize IL-20 activity. The efects of IL-20 or 7E on human corneal epithelial cells and mac‑
rophages under hyperosmotic stress were analyzed. 7E was topically applied to eyes to evaluate the therapeutic
efects in the DED animal models.
Results: IL-20 was signifcantly upregulated in the tears of patients with DED and in the tears and corneas of DED ani‑
mal models. Under hyperosmotic stress, IL-20 expression was induced via NFAT5 activation in corneal epithelial cells.
7E suppressed hyperosmotic stress-induced activation of macrophages. IL-20 induced cell death in corneal epithelial
cells and 7E protected cells from hyperosmotic stress-induced cell death. Blocking IL-20 signaling with 7E protected
mice from BAC-induced, LGE-induced, and DS-induced DED by reducing DED symptoms and inhibiting infammatory
responses, macrophage infltration, apoptosis, and Th17 populations in the conjunctiva and draining lymph nodes.
Conclusions: Our results demonstrated the functions of IL-20 in DED and presented a potential therapeutic option
for this condition. - 中文關鍵字:
- 英文關鍵字: Dry eye disease, Interleukin-20 (IL-20), Infammation, Hyperosmotic stress