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以体外牛晶状体和十二烷基硫酸钠作为化学模型的眼毒性机制

Mechanisms of ocular toxicity using the in vitro bovine lens and sodium dodecyl sulfate as a chemical model.

作者信息

Bantseev Vladimir, McCanna David, Banh Alice, Wong Winnie W, Moran Kelley L, Dixon D George, Trevithick John R, Sivak Jacob G

机构信息

School of Optometry and Department of Biology, University of Waterloo, Ontario, N2L 3G1 Canada.

出版信息

Toxicol Sci. 2003 May;73(1):98-107. doi: 10.1093/toxsci/kfg060. Epub 2003 Apr 15.

DOI:10.1093/toxsci/kfg060
PMID:12700424
Abstract

Previous work using the in vitro bovine lens as a model has shown a correlation between toxicity and lens optical function and showed much higher sensitivity in detecting irritancy of several surfactants at much lower concentrations than the Draize score. In the current study, cultured bovine lenses were used to study the effects of the surfactant sodium dodecyl sulfate (SDS) on lens optical properties and mitochondrial integrity. Bovine lenses were exposed to SDS (0.1 to 0.00625%) for 30 min and cultured for 24 h. Compared to controls (n = 17), loss of sharp focus was evident immediately following exposure to 0.1% SDS (n = 14, p < 0.0001). At 24 h loss of sharp focus became evident in all groups. Loss of lens transparency, significant increase in lens wet weight, and axial length were seen 24 h postexposure in lenses treated with 0.1 to 0.025% SDS. Confocal analysis 24 h postexposure showed SDS concentration-dependent decrease in number and length of the mitochondria in lens epithelial and superficial cortical fiber cells. The results of this study show a correlation between lens optical properties and metabolic function and together provide a sensitive in vitro model of ocular chemical toxicity. Results of confocal analysis suggest that the mitochondrial integrity of the superficial cortical fiber cells is most sensitive to damage caused by SDS. The results further suggest that recovery of lens metabolic function is necessary for the recovery of lens optical properties.

摘要

以往以体外牛晶状体为模型的研究表明,毒性与晶状体光学功能之间存在相关性,并且在检测几种表面活性剂的刺激性时,该模型在比Draize评分低得多的浓度下表现出更高的敏感性。在本研究中,使用培养的牛晶状体来研究表面活性剂十二烷基硫酸钠(SDS)对晶状体光学特性和线粒体完整性的影响。将牛晶状体暴露于SDS(0.1%至0.00625%)30分钟,然后培养24小时。与对照组(n = 17)相比,暴露于0.1% SDS后(n = 14,p < 0.0001),立即明显出现聚焦清晰度丧失。在24小时时,所有组均明显出现聚焦清晰度丧失。在用0.1%至0.025% SDS处理的晶状体中,暴露24小时后可见晶状体透明度丧失、晶状体湿重显著增加和轴向长度增加。暴露24小时后的共聚焦分析显示,SDS浓度依赖性地降低了晶状体上皮细胞和表层皮质纤维细胞中线粒体的数量和长度。本研究结果表明晶状体光学特性与代谢功能之间存在相关性,并共同提供了一种敏感的眼部化学毒性体外模型。共聚焦分析结果表明,表层皮质纤维细胞的线粒体完整性对SDS引起的损伤最为敏感。结果进一步表明,晶状体代谢功能的恢复对于晶状体光学特性的恢复是必要的。

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