D-β-hydroxybutyrate protects against corneal epithelial disorders in a rat dry eye model with jogging board
D-β-hydroxybutyrate protects against corneal epithelial disorders in a rat dry eye model with jogging board
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DOI：
10.1167/iovs.04-1344
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发表时间：
2005-07-01
影响因子：
4.4
通讯作者：
Tsubota, K
中科院分区：
文献类型：
--
作者：
Nakamura, S;Shibuya, M;Tsubota, K
目的。本研究旨在通过诱导不适当的泪液动力学和眨眼频率变化，建立大鼠角膜上皮病变干眼模型。研究了d - β -羟基丁酸酯（HBA）对角膜上皮细胞的保护作用。在持续暴露于低湿度气流下进行一系列处理。将大鼠置于塑料管制成的慢跑板（JB）上7.5 h/d，在单独的笼子中放置16.5 h，不进行JB处理。然后分析泪液动力学和角膜上皮结构的变化。治疗5天后，观察角膜荧光素染色的大鼠，在JB治疗期间，每天4次滴入含80 mM HBA的滴眼液，观察HBA的作用。在JB治疗期间，在几乎一半角膜表面出现持续点状染色的眼睛中，眨眼频率、Schirmer评分和泪液清除率显著降低。与初始或磷酸盐缓冲盐水处理的眼睛相比，使用含hba滴眼液可显著减少点状染色。该大鼠干眼模型通过在干燥条件下反复使用JB建立，诱导了与人类相似的泪液动力学异常和浅表点状角膜病变。这些发现提示HBA在中度至轻度干眼症患者角膜表面上皮疾病中的潜在临床应用。
Purpose. The purpose of this study was to establish a rat dry eye model of corneal epithelial disorders by inducing improper tear dynamics and change in blink frequency. The protective effect of D-beta-hydroxybutyrate (HBA) on the corneal epithelia was also investigated.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 JB treatment. The resultant changes in tear dynamics and corneal epithelial structure were then analyzed. Five days after the rats were exposed to the treatment, eyes that showed corneal fluorescein staining were examined, to investigate the effect of HBA, by administration of eye drops containing 80 mM HBA four times daily during JB treatment for 5 days.Results. Significant reductions in blink frequency, Schirmer score, and tear clearance were recorded during JB treatment in eyes that showed persistent punctate staining of almost one half of the corneal surface. The application of HBA-containing eye drops significantly reduced the punctate staining compared with the initial or phosphate-buffered saline-treated eyes.Conclusions. This rat dry eye model, established by repeated JB treatment in desiccating conditions, induced abnormal tear dynamics and superficial punctate keratopathy similar to that in humans. These findings suggest the potential clinical application of HBA in corneal surface epithelial disorders in patients with moderate to mild dry eye.