The Impact of Type 1 Diabetes Mellitus on Corneal Epithelial Nerve Morphology and the Corneal Epithelium
The Impact of Type 1 Diabetes Mellitus on Corneal Epithelial Nerve Morphology and the Corneal Epithelium
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DOI：
10.1016/j.ajpath.2014.06.016
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发表时间：
2014-10-01
影响因子：
6
通讯作者：
Robertson, Danielle M.
中科院分区：
文献类型：
--
作者：
Cai, Daniel;Zhu, Meifang;Robertson, Danielle M.
糖尿病角膜神经病变可导致慢性、威胁视力的角膜病变。尽管确切的病因尚不清楚，但据信角膜敏感性的降低和神经营养支持的丧失会导致角膜疾病。关于神经损失和对角膜上皮的影响之间的关系的信息是有限的。我们使用链脲佐菌素诱导的糖尿病小鼠模型体内和原位三维成像研究了角膜上皮和神经形态的变化。链脲佐菌素治疗的小鼠表现出血糖水平升高和生长迟缓，这与严重糖尿病状态一致。患病 6 周后，基底下神经丛的长度明显减少。基底下神经丛的丧失与角膜上皮变薄和基底上皮细胞密度降低有关。相反，终末上皮神经的损失与动物年龄相关。重要的是，这是第一个 1 型糖尿病啮齿动物模型，显示出角膜上皮变薄和基底上皮细胞密度降低的特征，这两种特征此前已在患有糖尿病角膜神经病变的人类中得到记录。这些发现表明，在 1 型糖尿病中，在终末上皮神经丧失之前，基底下神经丛中的神经纤维损伤是明显的，来自基底下神经丛和终末上皮神经的神经营养支持对于维持角膜上皮稳态至关重要。
Diabetic corneal neuropathy can result in chronic, sight-threatening corneal pathology. Although the exact etiology is unknown, it is believed that a reduction in corneal sensitivity and Loss of neurotrophic support contributes to corneal disease. Information regarding the relationship between nerve Loss and effects on the corneal epithelium is limited. We investigated changes in the corneal epithelium and nerve morphology using three-dimensional imaging in vivo and in situ in a streptozotocin-induced diabetic mouse model. Streptozotocin-treated mice showed increased Levels of serum glucose and growth retardation consistent with a severe diabetic state. A reduction in the Length of the subbasal nerve plexus was evident after 6 weeks of disease. Loss of the subbasal nerve plexus was associated with corneal epithelial thinning and a reduction in basal epithelial cell density. In contrast, Loss of the terminal epithelial nerves was associated with animal age. Importantly, this is the first rodent model of type 1 diabetes that shows characteristics of corneal epithelial thinning and a reduction in basal epithelial cell density, both previously have been documented in humans with diabetic corneal neuropathy. These findings indicate that in type 1 diabetes, nerve fiber damage is evident in the subbasal nerve plexus before terminal epithelial nerve loss and that neurotrophic support from both the subbasal nerve plexus and terminal epithelial nerves is essential for the maintenance of corneal epithelial homeostasis.