Involvement of oxidative stress on corneal epithelial alterations in a blink-suppressed dry eye
Involvement of oxidative stress on corneal epithelial alterations in a blink-suppressed dry eye
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DOI：
10.1167/iovs.06-1027
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发表时间：
2007-04-01
影响因子：
4.4
通讯作者：
Tsubota, Kazuo
中科院分区：
文献类型：
--
作者：
Nakamura, Shigeru;Shibuya, Michiko;Tsubota, Kazuo
目的。在一个临床相关的活体大鼠模型中，研究氧化应激是否参与了眨眼抑制干眼角膜疾病的病因。方法：在持续暴露于低湿度气流的情况下进行一系列治疗。将大鼠放置在塑料管制成的慢跑板(JB)上，每天7.5h，并将它们放在没有JB的单独笼子中16.5h。这一方案重复了长达30天。用点状荧光素染色记分评价角膜表面改变。用8-羟基-2-脱氧鸟苷、4-羟基-2-脱氧鸟苷和丙二醛特异性抗体，用免疫组织化学方法检测角膜上皮细胞DNA损伤和活性醛对蛋白质修饰的影响。结果术后第1~30天，角膜上皮细胞荧光素染色积分明显增加。在整个实验过程中，干眼组在所有时间点的平均得分都显著高于未治疗组。干眼治疗中AFT氧化应激标志物的免疫反应性增加。染色阳性细胞的定量分析显示，干眼治疗后10天和30天的阳性细胞数明显多于非干眼治疗组。结论：这些结果提示，在眨眼抑制的干眼中，氧化应激的积累与角膜上皮病变的病因有关。
PURPOSE. To investigate whether oxidative stress is involved in the etiology of the corneal disorder in blink-suppressed dry eye in a clinically relevant in vivo rat model.METHODS. A series of treatments were performed under continuous exposure to low-humidity airflow. Rats were placed on a jogging board (JB) made of a plastic pipe for 7.5 h/d, and for 16.5 hours, they were placed in individual cages without a JB. This protocol was repeated for up to 30 days. Corneal surface alteration was evaluated by the score of punctate fluorescein staining. To assess oxidative stress status, the levels of damaged DNA, and the protein modification by reactive aldehydes in corneal epithelia were detected by immunohistochemistry, Using 8-hydroxy-2-deoxyguanosine, 4-hydroxynonenal- and malondialdehyde-specific antibodies.RESULTS. Significant increases in the fluorescein staining score were observed from days 1 to 30 compared with the initial value. The average score for the dry eye group was significantly increased compared with that for the nontreatment group at all time points throughout the experiment. Immunoreactivity of aft oxidative stress markers increased in the dry eye treatment. Quantitative analysis of the positive-stained cells showed a significant increase in the number of positive cells after 10 and 30 days in the dry eye treatment group compared with the nontreatment group.CONCLUSIONS. These results suggest a relationship between the accumulation of oxidative stress and the etiology of corneal epithelial alterations in blink-suppressed dry eye.