GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, Karnataka, India; Department of Integrative Biology, School of Biosciences and Technology, VIT University Vellore, Tamil Nadu, 632014, India.
GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, Karnataka, India.
Ocul Surf. 2019 Oct;17(4):699-713. doi: 10.1016/j.jtos.2019.08.004. Epub 2019 Aug 11.
Cornea acts as a structural barrier and protects the eye from environmental stresses. Inflammation in ocular surface causes discomfort and visual distortion. Defective autophagy has been associated with inflammation and ocular surface diseases. Therefore, we explored the protective role of trehalose on inflammation and desiccation-triggered stress in human corneal cells in vitro and in dry eye patients.
TNF-α and desiccation stress induced human corneal cells (piHCF and HCE-T) with or without trehalose treatment were analyzed for the expression levels of inflammatory and autophagy related markers by qPCR, western blotting, multiplex ELISA and fluorescence imaging. Dry eye patients (N = 9) were enrolled and administered with trehalose in one eye and carboxymethylcellulose (CMC) in the contralateral eye (B.I.D, for 30 days). Dry eye signs OSDI, TBUT, Schirmer's Test, and tear cytokines were measured in dry eye patient's pre and post treatment.
Cells treated with trehalose exhibits increased levels of autophagy markers LC3II and LAMP1 compared to untreated cells. Trehalose reduced the mRNA and secreted cytokines levels of IL-6, IL-8 and MCP-1 in corneal cells under TNF-α and desiccation stress mediated inflammation compared to controls. Further, trehalose reduced stress driven p38 phosphorylation in corneal cells. Additionally, topical administration of trehalose alleviated the clinical symptoms and tears cytokine levels in dry eye patients compared to CMC.
Trehalose reduces stress induced inflammation through p38MAPK inhibition and autophagy activation. The anti-inflammatory mechanism of trehalose was independent to NFκB pathway. Further, topical administration of trehalose ameliorated dry eye associated symptoms and associated tear cytokines levels.
角膜作为一种结构屏障，保护眼睛免受环境压力的影响。眼表面炎症会引起不适和视觉扭曲。已发现自噬缺陷与炎症和眼表面疾病有关。因此，我们在体外和干眼症患者中探索了海藻糖对人角膜细胞炎症和干燥引发的应激的保护作用。
用 TNF-α和干燥应激诱导含或不含海藻糖处理的人角膜细胞（piHCF 和 HCE-T），通过 qPCR、Western blot、多重 ELISA 和荧光成像分析炎症和自噬相关标志物的表达水平。招募了 9 例干眼症患者，在一只眼给予海藻糖，在对侧眼给予羧甲基纤维素（CMC）（B.I.D，持续 30 天）。在治疗前和治疗后测量干眼症患者的干眼症状 OSDI、TBUT、Schirmer 测试和泪液细胞因子。
与未处理的细胞相比，用海藻糖处理的细胞表现出自噬标志物 LC3II 和 LAMP1 的水平增加。与对照组相比，海藻糖降低了 TNF-α和干燥应激介导的炎症下角膜细胞中 IL-6、IL-8 和 MCP-1 的 mRNA 和分泌细胞因子水平。此外，海藻糖降低了角膜细胞中应激驱动的 p38 磷酸化。此外，与 CMC 相比，局部给予海藻糖可减轻干眼症患者的临床症状和泪液细胞因子水平。
海藻糖通过抑制 p38MAPK 和激活自噬来减轻应激引起的炎症。海藻糖的抗炎机制与 NFκB 途径无关。此外，局部给予海藻糖可改善干眼症相关症状和相关泪液细胞因子水平。
