PDF(Pubmed)
Abstract：
Dry eye disease (DED) is a growing health concern that impacts millions of individuals every year, and is associated with corneal injury, excessive oxidative stress and inflammation. Current therapeutic strategies, including artificial tears and anti-inflammatory agents, are unable to achieve a permanent clinical cure due to their temporary nature or adverse side effects. Therefore, here, we investigated the effectiveness of the topical administration of programmed death-ligand 1 (PD-L1) in the mouse model of DED. The model was generated in C57BL/6 mice by excising the extra orbital lacrimal gland and causing desiccation stress with scopolamine injections. Subsequently, either phosphate-buffered saline (3 µL/eye) or PD-L1 (0.5 µg/mL) was topically administered for 10 days. Tear volume was evaluated with phenol red thread, and corneal fluorescein staining was observed to quantify the corneal epithelial defect. Corneas were collected for histological analysis, and the expression levels of inflammatory signaling proteins such as CD4, CD3e, IL-17, IL-1β, pIkB-α, pNF-kB and pERK1/2 were assessed through immunofluorescence and Western blot techniques. Our results demonstrate that desiccating stress-induced corneal epithelial defect and tear secretion were significantly improved by topical PD-L1 and could reduce corneal CD4+ T cell infiltration, inflammation and apoptosis in a DED mouse model by downregulating IL-17 production and ERK1/2-NFkB pathways.
摘要：
干眼症（DED）是一种日益增长的健康问题，每年影响数百万人，并与角膜损伤有关，过度的氧化应激和炎症。目前的治疗策略，包括人工泪液和抗炎药,由于其暂时性或不良副作用，无法实现永久性临床治愈。因此,在这里，我们研究了在DED小鼠模型中局部施用程序性死亡配体1(PD-L1)的有效性.在C57BL/6小鼠中通过切除眶外泪腺并使用东pol碱注射引起干燥应激来产生模型。随后，磷酸盐缓冲盐水(3µL/眼)或PD-L1(0.5µg/mL)局部给药10天.用酚红线评价泪液体积,观察角膜荧光素染色以定量角膜上皮缺损。收集角膜进行组织学分析，和炎症信号蛋白如CD4，CD3e的表达水平，IL-17，IL-1β，pIkB-α,通过免疫荧光和蛋白质印迹技术评估pNF-kB和pERK1/2。我们的结果表明，局部PD-L1可显着改善干燥应激诱导的角膜上皮缺损和泪液分泌，并可以减少角膜CD4T细胞浸润，通过下调IL-17产生和ERK1/2-NFkB途径在DED小鼠模型中的炎症和凋亡。
