■本研究的目的是探讨异位脑胺的保护作用和潜在机制,一种天然的渗透保护剂,干眼症眼表粘蛋白的产生。
■在暴露于干燥应激(DS)的C57BL/6小鼠中建立干眼模型,未处理(UT)小鼠作为对照。DS小鼠用2.0%艾克托因或PBS载体局部处理。通过俄勒冈绿葡聚糖(OGD)荧光染色评估角膜上皮缺损。结膜杯状细胞,眼粘蛋白,和T帮助(Th)细胞因子通过免疫荧光染色或ELISA进行评估,和RT-qPCR。
■与UT小鼠相比,角膜上皮缺损被检测为强点OGD荧光染色DS小鼠与载体,而ectoine治疗将OGD染色大大降低至接近正常水平。DS小鼠结膜杯状细胞密度和细胞大小明显下降,但通过艾克托因治疗显着恢复。两种凝胶分泌型MUC5AC和MUC2的蛋白质产生和mRNA表达,以及4种跨膜粘蛋白,MUC1,MUC4,MUC16和MUC15在DS小鼠中大幅下降,但是被ectoine修复了。此外,Th2细胞因子IL-13被抑制,而Th1细胞因子IFN-γ在DS小鼠的结膜和引流颈淋巴结(CLN)中的蛋白质和mRNA水平受到刺激,导致IL-13/IFN-γ比值降低。有趣的是,2.0%的埃托因逆转了它们的交替,并恢复了IL-13/IFN-γ平衡。
■我们的研究结果表明,外用外用能显著减少角膜损伤,并通过恢复小鼠干眼模型中不平衡的IL-13/IFN-γ信号传导来增强杯状细胞密度和粘蛋白产生。这表明天然渗透保护剂艾托因治疗干眼病的潜力。
UNASSIGNED: This study aimed to explore protective effects and potential mechanism of ectoine, a natural osmoprotectant, on ocular surface mucin production in dry eye disease.
UNASSIGNED: A dry eye model was established in C57BL/6 mice exposed to desiccating stress (DS) with untreated (UT) mice as controls. DS mice were topically treated with 2.0% ectoine or PBS vehicle. Corneal epithelial defects were assessed by Oregon Green Dextran (OGD) fluorescent staining. Conjunctival goblet cells, ocular mucins, and T help (Th) cytokines were evaluated by immunofluorescent staining or ELISA, and RT-qPCR.
UNASSIGNED: Compared with UT mice, corneal epithelial defects were detected as strong punctate OGD fluorescent staining in DS mice with vehicle, whereas ectoine treatment largely reduced OGD staining to near-normal levels. Conjunctival goblet cell density and cell size decreased markedly in DS mice, but was significantly recovered by ectoine treatment. The protein production and mRNA expression of two gel-forming secreted MUC5AC and MUC2, and 4 transmembrane mucins, MUC1, MUC4, MUC16, and MUC15, largely decreased in DS mice, but was restored by ectoine. Furthermore, Th2 cytokine IL-13 was inhibited, whereas Th1 cytokine IFN-γ was stimulated at protein and mRNA levels in conjunctiva and draining cervical lymph nodes (CLNs) of DS mice, leading to decreased IL-13/IFN-γ ratio. Interestingly, 2.0% ectoine reversed their alternations and restored IL-13/IFN-γ balance.
UNASSIGNED: Our findings demonstrate that topical ectoine significantly reduces corneal damage, and enhances goblet cell density and mucin production through restoring imbalanced IL-13/IFN-γ signaling in murine dry eye model. This suggests therapeutic potential of natural osmoprotectant ectoine for dry eye disease.