Research on the stability of a rabbit dry eye model induced by topical application of the preservative benzalkonium chloride.
Research on the stability of a rabbit dry eye model induced by topical application of the preservative benzalkonium chloride.
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局部应用防腐剂苯扎氯铵诱导兔干眼模型的稳定性研究
DOI：
10.1371/journal.pone.0033688
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Li C;Song Y;Luan S;Wan P;Li N;Tang J;Han Y;Xiong C;Wang Z
干眼症是全球一种常见疾病，动物模型对其研究至关重要。目前，尚无关于现有动物模型稳定性的研究，这可能对以往的干眼症研究产生负面影响。在本研究中，我们观察了局部应用苯扎氯铵（BAC）诱导的兔干眼症模型的稳定性，并确定了该模型的有效时间。
80只白兔随机分为4组。每只兔子随机选取一只眼睛，分别接受0.1% BAC局部滴眼，每天2次，持续2周（BAC - W2组）、3周（BAC - W3组）、4周（BAC - W4组）或5周（BAC - W5组）。在BAC处理前（正常）以及BAC去除后第0、7、14和21天进行荧光素染色、泪液分泌试验（Schirmer's tests）和结膜印迹细胞学检查。在这些时间点采集眼球进行免疫荧光染色、苏木精 - 伊红（HE）染色和电子显微镜检查。去除BAC后，BAC - W2组的干眼症体征持续1周。与正常组相比，BAC - W3组和BAC - W4组在第7天（P < 0.05）以及BAC - W5组在第14天（P < 0.05），泪液分泌试验和荧光素染色结果仍存在显著差异。在所有时间点，3个实验组的杯状细胞密度下降情况保持稳定（P < 0.001）。在BAC - W4组，尤其是BAC - W5组，直至第21天，均可观察到黏蛋白 - 5 AC亚型（MUC5AC）水平下降，以及角膜和结膜的组织病理学和超微结构紊乱。
局部应用0.1% BAC 5周可诱导出稳定的兔干眼症模型，去除BAC后，干眼症体征可持续2周（对于混合型干眼症）或至少3周（对于黏蛋白缺乏型干眼症）。
Background Dry eye is a common disease worldwide, and animal models are critical for the study of it. At present, there is no research about the stability of the extant animal models, which may have negative implications for previous dry eye studies. In this study, we observed the stability of a rabbit dry eye model induced by the topical benzalkonium chloride (BAC) and determined the valid time of this model. Methods and Findings Eighty white rabbits were randomly divided into four groups. One eye from each rabbit was randomly chosen to receive topical 0.1% BAC twice daily for 2 weeks (Group BAC-W2), 3 weeks (Group BAC-W3), 4 weeks (Group BAC-W4), or 5 weeks (Group BAC-W5). Fluorescein staining, Schirmer's tests, and conjunctival impression cytology were performed before BAC treatment (normal) and on days 0, 7, 14 and 21 after BAC removal. The eyeballs were collected at these time points for immunofluorescence staining, hematoxylin and eosin (HE) staining, and electron microscopy. After removing BAC, the signs of dry eye in Group BAC-W2 lasted one week. Compared with normal, there were still significant differences in the results of Schirmer's tests and fluorescein staining in Groups BAC-W3 and BAC-W4 on day 7 (P<0.05) and in Group BAC-W5 on day 14 (P<0.05). Decreases in goblet cell density remained stable in the three experimental groups at all time points (P<0.001). Decreased levels of mucin-5 subtype AC (MUC5AC), along with histopathological and ultrastructural disorders of the cornea and conjunctiva could be observed in Group BAC-W4 and particularly in Group BAC-W5 until day 21. Conclusions A stable rabbit dry eye model was induced by topical 0.1% BAC for 5 weeks, and after BAC removal, the signs of dry eye were sustained for 2 weeks (for the mixed type of dry eye) or for at least 3 weeks (for mucin-deficient dry eye).
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影响因子：
2
作者：
Ishibashi, T;Yokoi, N;Kinoshita, S
通讯作者：
Kinoshita, S
影响因子：
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通讯作者：
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影响因子：
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作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
SHIRASAWA, E