The ocular anomalies in a cystinosis animal model mimic disease pathogenesis
The ocular anomalies in a cystinosis animal model mimic disease pathogenesis
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DOI：
10.1203/pdr.0b013e31809fda89
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发表时间：
2007-08-01
影响因子：
3.6
通讯作者：
Kremer, Eric J.
中科院分区：
文献类型：
--
作者：
Kalatzis, Vasiliki;Serratrice, Nicolas;Kremer, Eric J.
胱氨酸病是一种以胱氨酸异常积累为特征的溶酶体储存疾病，其在高浓度下形成晶体。致病基因CTNS编码胱氨酸蛋白，溶酶体胱氨酸转运蛋白。眼睛是最先受到影响的器官之一（在生命的第一个十年中出现角膜病变和视神经恐惧症，在第二个十年中出现视力障碍）。我们描述了Ctns（-/-）小鼠的眼部异常，以确定它们是否模仿患者的眼部异常。在Ctns（-/-）小鼠的虹膜、睫状体和角膜中观察到最显著的胱氨酸蓄积。一致地，Ctns（-/-）小鼠具有低眼内压（IOP），并且似乎轻度恐惧。视网膜胱氨酸水平升高，但随着年龄的增长而增加不太明显。一致的是，视网膜是完整的，视网膜电图（ERG）的配置文件是正常的小鼠年龄小于19个月，超过这个年龄，视网膜晶体和病变出现。最后，透镜含有最低的胱氨酸水平，未观察到晶体。Ctns（-/-）小鼠中胱氨酸蓄积的时空模式与患者的时空模式相似，并验证了小鼠作为胱氨酸病眼部异常的模型。这项工作是测试新型眼部胱氨酸耗竭疗法的先决条件。
Cystinosis is a lysosomal storage disorder characterized by abnormal accumulation of cystine, which forms crystals at high concentrations. The causative gene CTNS encodes cystinosin, the lysosomal cystine transporter. The eye is one of the first organs affected (corneal lesions and photophobia in the first and visual impairment in the second decade of life). We characterized the ocular anomalies of Ctns(-/-) mice to determine whether they mimic those of patients. The most dramatic cystine accumulation was seen in the iris, ciliary body, and cornea of Ctns(-/-) mice. Consistently, Ctns(-/-) mice had a low intraocular pressure (IOP) and seemed mildly photophobic. Retinal cystine levels were elevated but increased less dramatically with age. Consistently, the retina was intact and electroretinogram (ERG) profiles were normal in mice younger than 19 mo; beyond this age, retinal crystals and lesions appeared. Finally, the lens contained the lowest cystine levels and crystals were not seen. The temporospatial pattern of cystine accumulation in Ctns(-/-) mice parallels that of patients and validates the mice as a model for the ocular anomalies of cystinosis. This work is a prerequisite step to the testing of novel ocular cystine-depleting therapies.