Shen Jiachao, Liang Yan, Bi Zhaojing, Yin Xin, Chen Chen, Zhao Xinmei, Liu Shujun, Li Yuanbin
Department of Ophthalmology, Binzhou Medical College, Yantai, 264000, China; Department of Ophthalmology, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, 264000, China.
Department of Ophthalmology, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, 264000, China.
Exp Eye Res. 2023 Apr;229:109418. doi: 10.1016/j.exer.2023.109418. Epub 2023 Feb 16.
Hyperosmolarity is closely related to dry eye disease (DED), which induces corneal epithelial cell structure and dysfunction leading to ocular surface inflammation. Cyclosporine A (CSA) is a cyclopeptide consisting of 11 deduced amino acids. It has an immunosuppressive effect and shows a vital function in inhibiting the inflammatory response. The mechanism of CSA in DED is still not entirely clear. This experiment aimed to investigate the possible mechanism of CSA in the hyperosmotic DED model. This study found that CSA can inhibit the transcript levels of DED high mobility group protein 1 (HMGB1), Toll-like receptor 4 (TLR4) and nuclear transcription factor κB (NF-κB) in signaling pathways. In addition, the study also found that 550 mOsm/L can induce the formation of DED models in vivo or in vitro. Furthermore, different concentrations of CSA have different effects on the expression of HMGB1 in human corneal epithelial cells under hyperosmotic stimulation, and high concentrations of CSA may increase the expression of HMGB1. In addition, CSA effectively reduced the corneal fluorescence staining score of the DE group and increased the tear volume of mice. Therefore, this experimental investigation might supply new evidence for the mechanism of CSA in DED, provide a potential new therapy for treating DED, and provide a theoretical basis for CSA treatment of DED.
高渗与干眼病（DED）密切相关，干眼病会导致角膜上皮细胞结构和功能障碍，进而引发眼表炎症。环孢素A（CSA）是一种由11个推导氨基酸组成的环肽。它具有免疫抑制作用，在抑制炎症反应中发挥着重要作用。CSA在DED中的作用机制仍不完全清楚。本实验旨在研究CSA在高渗性DED模型中的可能机制。本研究发现，CSA可以抑制DED高迁移率族蛋白1（HMGB1）、Toll样受体4（TLR4）和核转录因子κB（NF-κB）在信号通路中的转录水平。此外，研究还发现550 mOsm/L可在体内或体外诱导DED模型的形成。此外，不同浓度的CSA对高渗刺激下人角膜上皮细胞中HMGB1的表达有不同影响，高浓度的CSA可能会增加HMGB1的表达。此外，CSA有效降低了DED组的角膜荧光染色评分，并增加了小鼠的泪液量。因此，本实验研究可能为CSA在DED中的作用机制提供新的证据，为治疗DED提供潜在的新疗法，并为CSA治疗DED提供理论依据。
