Changes in Corneal Innervation and Sensitivity and Acetylcholine-Mediated Vascular Relaxation of the Posterior Ciliary Artery in a Type 2 Diabetic Rat
Changes in Corneal Innervation and Sensitivity and Acetylcholine-Mediated Vascular Relaxation of the Posterior Ciliary Artery in a Type 2 Diabetic Rat
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DOI：
10.1167/iovs.11-8806
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发表时间：
2012-03-01
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.角膜共聚焦显微镜是一种新兴的临床工具，以评估糖尿病神经病变的发展和进展。这些研究的目的是描述2型糖尿病大鼠模型中角膜敏感性和神经支配的变化与标准周围神经病变终点的关系。在动物模型中评估糖尿病引起的角膜神经支配和敏感性的变化对于确定角膜标记物用于临床前研究以测试糖尿病神经病的潜在新治疗方法的有用性将是重要的。高脂/低剂量链脲佐菌素糖尿病大鼠用于检查糖尿病诱导的标准糖尿病神经病变终点的变化，使用共焦显微镜检查角膜的神经支配，使用Cochet-Bonnet触觉计检查角膜敏感性，以及后睫状动脉的血管反应性。与年龄匹配的对照组大鼠相比，高脂饮食诱导大鼠高血糖引起神经传导速度下降，热痛觉减退，和表皮内神经纤维轮廓。在角膜中，角膜神经纤维长度和敏感性降低。此外，睫状后动脉对乙酰胆碱的反应性血管舒张降低。这些研究表明，在2型糖尿病大鼠模型中，角膜神经支配和敏感性的变化与糖尿病患者中观察到的变化一致。角膜敏感性和神经支配可能是临床前研究中检查糖尿病神经病变潜在治疗的有价值的终点。（Invest Ophthalmol维斯科学。2012;53：1182-1187）DOI：10.1167/iovs.11-8806
PURPOSE. Corneal 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 changes in corneal sensitivity and innervation in a rat model of type 2 diabetes in relation to standard peripheral neuropathy endpoints. Assessment of diabetes-induced changes in corneal innervation and sensitivity in animal models will be important for determining the usefulness of corneal markers for preclinical studies to test potential new treatments for diabetic neuropathy.METHODS. High-fat/low-dose streptozotocin diabetic rats were used to examine diabetes-induced changes in standard diabetic neuropathy endpoints and innervation of the cornea using confocal microscopy, corneal sensitivity using a Cochet-Bonnet esthesiometer, and vascular reactivity of the posterior ciliary artery.RESULTS. Compared with age-matched control rats, the induction of hyperglycemia in rats fed high-fat diets caused a decrease in nerve conduction velocity, thermal hypoalgesia, and intraepidermal nerve fiber profiles. In the cornea there was a decrease in corneal nerve fiber length and sensitivity. In addition, vascular relaxation in response to acetylcholine was decreased in the posterior ciliary artery.CONCLUSIONS. These studies suggest that in a type 2 diabetic rat model, changes in corneal nerve innervation and sensitivity occur that are consistent with changes seen in diabetic patients. Corneal sensitivity and innervation may be valuable endpoints for examining the potential treatments of diabetic neuropathy in preclinical studies. (Invest Ophthalmol Vis Sci. 2012;53:1182-1187) DOI:10.1167/iovs.11-8806