Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis
Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis
复制标题
DOI：
10.1016/j.exer.2009.03.015
复制
发表时间：
2009-09-01
影响因子：
3.4
通讯作者：
Qu, Jia
中科院分区：
文献类型：
--
作者：
Chen, Wei;Zhang, Xiaobo;Qu, Jia
二糖海藻糖是许多生物体中参与耐脱水性（在几乎完全脱水的情况下存活的能力）的关键成分。它的存在还通过保护蛋白质和膜免受变性，使细菌和人类细胞具有抵抗干燥和高渗透压的能力。本研究使用一种由可控低湿度气流诱导的新型小鼠干眼模型，以确定局部应用海藻糖是否能够治愈由眼表干燥引起的眼表上皮疾病。此外，还将87.6 mM海藻糖滴眼液的疗效与20%血清的疗效进行了比较，血清的疗效已有充分记录。通过在智能控制环境系统（ICES）中将小鼠眼睛暴露于持续可控的低湿度气流中21天来诱导小鼠眼表上皮疾病，这加速了泪液蒸发。然后将小鼠随机分为三组：对照组接受PBS（0.01M）治疗；第二组接受87.6 mM海藻糖滴眼液治疗；第三组接受小鼠血清滴眼液治疗。每种治疗均以10 μl剂量每6小时给药一次，持续14天。分析了角膜屏障功能的变化以及角膜和结膜的组织病理学检查结果，并使用活性caspase - 3评估了眼表的细胞凋亡水平。治疗14天后，与接受血清和PBS治疗的眼睛相比，接受海藻糖治疗的眼睛的角膜荧光素染色面积、角膜上皮顶端的褶皱和脱屑细胞以及眼表上皮的凋亡细胞均显著减少。相比之下，治疗14天后，与血清相比，接受海藻糖治疗的眼睛在角膜上皮厚度、结膜上皮鳞状化生以及结膜杯状细胞数量方面的改善不太明显。这些结果表明，海藻糖可通过抑制细胞凋亡改善因干燥导致的眼表上皮疾病的外观。局部应用时，海藻糖产生一些与血清相同的反应，并能维持角膜健康。（c）2009 Elsevier Ltd.保留所有权利。
The disaccharide trehalose is a key element involved in anhydrobiosis (the capability of surviving almost complete dehydration) in many organisms. Its presence also confers resistance to desiccation and high osmolarity in bacterial and human cells by protecting proteins and membranes from denaturation. The present study used a novel murine dry eye model induced by controlled low-humidity air velocity to determine whether topically applied trehalose could heal ocular surface epithelial disorders caused by ocular surface desiccation. In addition, the efficacy of 87.6 mM trehalose eyedrops was compared with that of 20% serum, the efficacy of which has been well documented. Mice ocular surface epithelial disorders were induced by exposure of murine eyes to continuous controlled low-humidity air velocity in an intelligently controlled environmental system (ICES) for 21 days, which accelerated the tear evaporation. The mice were then randomized into three groups: the control group received PBS (0.01M) treatment; a second group received 87.6 mM trehalose eyedrops treatment; and the third group received mice serum eyedrops treatment. Each treatment was administered as a 10 mu l dose every 6 h for 14 days. The resultant changes in corneal barrier function and histopathologic examination of cornea and conjunctiva were analyzed and the level of apoptosis on the ocular surface was assessed using active caspase-3. After 14 days of treatment, the corneal fluorescein staining area, the ruffling and desquamating cells on the apical corneal epithelium, as well as the apoptotic cells on ocular surface epithelium had significantly reduced in eyes treated with trehalose compared with those treated with serum and PBS. In contrast, after 14 days of treatment, improvements in the thickness of the corneal epithelium, the squamous metaplasia in conjunctival epithelium and the number of goblet cells of the conjunctiva were less marked in eyes treated with trehalose compared with serum. These results demonstrated that trehalose could improve the appearance of ocular surface epithelial disorders due to desiccation through suppression of apoptosis. Trehalose produces some of the same responses as serum upon topical application and can maintain corneal health. (c) 2009 Elsevier Ltd. All rights reserved.