Early Loss of Innervation of Cornea Epithelium in Streptozotocin-Induced Type 1 Diabetic Rats: Improvement with Ilepatril Treatment
Early Loss of Innervation of Cornea Epithelium in Streptozotocin-Induced Type 1 Diabetic Rats: Improvement with Ilepatril Treatment
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DOI：
10.1167/iovs.12-10826
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发表时间：
2012-12-01
影响因子：
4.4
通讯作者：
Yorek, Mark A.
中科院分区：
文献类型：
--
作者：
Davidson, Eric P.;Coppey, Lawrence J.;Yorek, Mark A.
目的。角膜共聚焦显微镜正在成为一种评估糖尿病神经病变发展和进展的临床工具。这些研究的目的是描述与标准周围神经病变终点相关的1型糖尿病大鼠模型早期角膜敏感性和神经支配的变化，并评估血管肽酶抑制剂伊莱帕尔对这些终点的影响。方法：链脲佐菌素-糖尿病大鼠8周，在实验期的最后6周接受或不使用伊莱帕利治疗。然后检测标准的糖尿病神经病变终点、角膜基底下神经和上皮神经支配、Cochet-Bonnet感觉仪的角膜敏感度和睫状后动脉的血管反应性。结果糖尿病引起神经传导速度减慢、热痛觉减退和表皮内神经纤维轮廓减少。在角膜中，支配角膜上皮的神经纤维减少，角膜敏感度降低，但角膜基底膜下神经纤维无变化。睫状后动脉对乙酰胆碱反应的血管舒张性降低。结论：这些研究表明，在1型糖尿病大鼠中，角膜上皮神经支配的减少发生在糖尿病早期，在可检测到的基础下角膜神经减少之前，这些和其他糖尿病神经病变相关的缺陷可以通过血管肽酶抑制剂部分或完全预防。(投资眼科VS科学。2012年；53：80678074)doi：10.1167/iovs.12-10826
PURPOSE. Cornea confocal microscopy is emerging as a clinical tool to evaluate the development and progression of diabetic neuropathy. The purpose of these studies was to characterize the early changes in corneal sensitivity and innervation in a rat model of type 1 diabetes in relation to standard peripheral neuropathy endpoints and to assess the effect of Ilepatril, a vasopeptidase inhibitor which blocks angiotensin converting enzyme and neutral endopeptidase, on these endpoints.METHODS. Streptozotocin-diabetic rats 8 weeks duration were treated with or without Ilepatril for the last 6 weeks of the experimental period. Afterwards, standard diabetic neuropathy endpoints, subbasal corneal nerves and innervation of the epithelium, corneal sensitivity using a Cochet-Bonnet esthesiometer, and vascular reactivity of the posterior ciliary artery were examined.RESULTS. Diabetes caused a decrease in nerve conduction velocity, thermal hypoalgesia, and a reduction in intraepidermal nerve fiber profiles. In the cornea there was a decrease in corneal nerve fibers innervating the epithelium and corneal sensitivity, but subbasal corneal nerve fibers was not changed. Vascular relaxation in response to acetylcholine was decreased in the posterior ciliary artery. These defects were partially to completely prevented by Ilepatril treatment.CONCLUSIONS. These studies suggest that in type 1 diabetic rats decreased innervation of the cornea epithelium occurs early in diabetes and prior to a detectable decrease in subbasal corneal nerves and that these and other diabetic neuropathy-related defects can be partially to completely prevented by a vasopeptidase inhibitor. (Invest Ophthalmol Vis Sci. 2012;53:8067-8074) DOI: 10.1167/iovs.12-10826