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壳聚糖-N-乙酰半胱氨酸共轭物在肉毒杆菌毒素B诱导的小鼠干眼模型中的作用

Effect of chitosan-N-acetylcysteine conjugate in a mouse model of botulinum toxin B-induced dry eye.

作者信息

Hongyok Teeravee, Chae Jemin J, Shin Young Joo, Na Daero, Li Li, Chuck Roy S

机构信息

Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland 21287, USA.

出版信息

Arch Ophthalmol. 2009 Apr;127(4):525-32. doi: 10.1001/archophthalmol.2009.52.

DOI:10.1001/archophthalmol.2009.52
PMID:19365035
Abstract

OBJECTIVE

To evaluate the effect of a thiolated polymer lubricant, chitosan-N-acetylcysteine conjugate (C-NAC), in a mouse model of dry eye.

METHODS

Eye drops containing 0.5% C-NAC, 0.3% C-NAC, a vehicle (control group), artificial tears, or fluorometholone were applied in a masked fashion in a mouse model of induced dry eye from 3 days to 4 weeks after botulinum toxin B injection. Corneal fluorescein staining was periodically recorded. Real-time reverse transcriptase-polymerase chain reaction and immunofluorescence staining were performed at the end of the study to evaluate inflammatory cytokine expressions.

RESULTS

Mice treated with C-NAC, 0.5%, and fluorometholone showed a downward trend that was not statistically significant in corneal staining compared with the other groups. Chitosan-NAC formulations, fluorometholone, and artificial tears significantly decreased IL-1beta (interleukin 1beta), IL-10, IL-12alpha, and tumor necrosis factor alpha expression in ocular surface tissues.

CONCLUSIONS

The botulinum toxin B-induced dry eye mouse model is potentially useful in evaluating new dry eye treatment. Evaluation of important molecular biomarkers suggests that C-NAC may impart some protective ocular surface properties. However, clinical data did not indicate statistically significant improvement of tear production and corneal staining in any of the groups tested.

CLINICAL RELEVANCE

Topically applied C-NAC might protect the ocular surface in dry eye syndrome, as evidenced by decreased inflammatory cytokine expression.

摘要

目的

在干眼小鼠模型中评估一种硫醇化聚合物润滑剂——壳聚糖-N-乙酰半胱氨酸共轭物(C-NAC)的效果。

方法

在肉毒杆菌毒素B注射后3天至4周的诱导性干眼小鼠模型中,以盲法应用含0.5% C-NAC、0.3% C-NAC的滴眼液、赋形剂(对照组)、人工泪液或氟米龙。定期记录角膜荧光素染色情况。在研究结束时进行实时逆转录聚合酶链反应和免疫荧光染色,以评估炎性细胞因子的表达。

结果

与其他组相比,用0.5% C-NAC和氟米龙治疗的小鼠角膜染色呈下降趋势,但无统计学意义。壳聚糖-NAC制剂、氟米龙和人工泪液显著降低了眼表组织中白细胞介素1β(IL-1β)、IL-10、IL-12α和肿瘤坏死因子α的表达。

结论

肉毒杆菌毒素B诱导的干眼小鼠模型在评估新的干眼治疗方法方面可能有用。对重要分子生物标志物的评估表明,C-NAC可能具有一些保护眼表的特性。然而,临床数据并未表明在任何测试组中泪液分泌和角膜染色有统计学意义的改善。

临床意义

局部应用C-NAC可能会保护干眼综合征的眼表,炎性细胞因子表达降低证明了这一点。

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