Hyperosmolarity is pro-inflammatory stress to the ocular surface epithelium associated with dry eye disease (DED). Astaxanthin (AST) is a kind of carotene, which exists in seafood and plays important roles in the amelioration of inflammatory diseases like arteriosclerosis, inflammatory bowel disease, sepsis, rheumatoid arthritis, gastric inflammation, brain inflammatory diseases. The aim of this study was to characterize the protective effect and potential mechanism of AST on DED in vitro and in vivo. Mouse models and human corneal epithelial cell (HCEC) cultures were exposed to hyperosmotic saline solution (HOSS) in in vitro and in vivo experiments, respectively. Experimental subjects were first pretreated with AST, and then the effect of the compound was assessed with clinical evaluation, real-time PCR (RT-PCR), western blot and immunofluorescent staining. We further investigated the possible mechanism of AST in DED by pre-treating with phosphoinositide 3-kinase inhibitor (LY294002). The addition of AST significantly reduced the expression of High-mobility group box 1 (HMGB1), as well as significantly inhibited the increases of TNF-α, IL-1β in a dose-dependent manner, but promoted the expression of phospho-Akt (p-Akt). BALB/c mice in DE group pretreated with AST showed significantly decreased corneal fluorescein staining scores. Moreover, pretreatment with LY294002 could eliminate the effects of AST preconditioning on the decrease of HMGB1. Our study provides evidence that AST could ameliorate DED which may be related to the inhibition of HMGB1, TNF-α, IL-1β, while PI3K/Akt signaling pathway may be involved in the expression of HMGB1 and the protective effect of AST preconditioning.

高渗性是与干眼病（DED）相关的眼表上皮的促炎性应激。虾青素（AST）是一种胡萝卜素，存在于海鲜中，在减轻炎症性疾病如动脉硬化，炎症性肠病，败血症，类风湿性关节炎，胃炎，脑炎性疾病中起重要作用。这项研究的目的是表征体外和体内AST对DED的保护作用和潜在机制。在体外和体内，将小鼠模型和人角膜上皮细胞（HCEC）培养物暴露于高渗盐溶液（HOSS）中实验。首先用AST对实验对象进行预处理，然后通过临床评估，实时PCR（RT-PCR），蛋白质印迹和免疫荧光染色评估该化合物的效果。我们通过用磷酸肌醇3-激酶抑制剂（LY294002）进行预处理，进一步研究了DED中AST的可能机制。AST的添加显着降低了高迁移率族1号框（HMGB1）的表达，并以剂量​​依赖的方式显着抑制了TNF-α，IL-1β的表达，但促进了磷酸化Akt（ p-Akt）。DE组经AST预处理的BALB / c小鼠的角膜荧光素染色评分显着降低。此外，用LY294002预处理可以消除AST预处理对HMGB1减少的影响。