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链脲佐菌素诱导的糖尿病小鼠视网膜神经细胞减少。

Decrease in retinal neuronal cells in streptozotocin-induced diabetic mice.

作者信息

Yang Yang, Mao Danna, Chen Xinke, Zhao Ling, Tian Qing, Liu Chenggang, Zhou Bo Lei Shanbi

机构信息

Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China.

出版信息

Mol Vis. 2012;18:1411-20. Epub 2012 Jun 1.

Abstract

PURPOSE

Little is known about retinal neuronal loss in the retinas of diabetic mice. The purpose of this study was the quantitative assessment of retinal neural cell number in diabetic mice.

METHODS

Five-week-old C57BL/6 mice were used as a diabetic model with streptozotocin. Mice were studied over the course of 6 and 12 weeks after the onset of diabetes. Intraocular pressure (IOP) was measured with a noninvasive TonoLab tonometer. The retinal ganglion cells (RGCs) were counted at two different time points after the induction of diabetes and examined using the immunofluorescence technique and quantitative analysis.

RESULTS

The diabetic mice had significantly elevated IOP levels at 6 and 12 weeks after the onset of diabetes compared with the age-matched control mice (p<0.01 and p<0.001, respectively). The temporal course of Brn3a+ RGC and Neuronal Nuclei+RGC (NeuN+ RGC) loss induced by intraperitoneal injection of streptozotocin followed a similar trend. At 6 and 12 weeks after the onset of diabetes, the number of Brn3a+ RGCs (p<0.05 at 6 weeks; p<0.001 at 12 weeks) and NeuN+ RGCs (p<0.05 at 6 weeks; p<0.001 at 12 weeks) was significantly lower in diabetic mice than age-matched control mice. In the retinal flatmounts, the number of Brn3a+ RGCs (p<0.05 at 6 weeks, p<0.01 at 12 weeks) was also significantly lower in diabetic mice than control mice. The IOP in diabetic mice was negatively related with RGCs in cross sections. The cut-off value of IOP was 14.2 mmHg for diabetes.

CONCLUSIONS

This is a specific quantitative study of neural cell loss in the retina during diabetes. These data suggest that retinal neural cell reduction occurs in diabetic mice. It indicates that RGC loss may be an important component of diabetic retinopathy.

摘要

目的

关于糖尿病小鼠视网膜中视网膜神经元丢失的情况,人们了解甚少。本研究的目的是对糖尿病小鼠视网膜神经细胞数量进行定量评估。

方法

将5周龄的C57BL/6小鼠用作链脲佐菌素诱导的糖尿病模型。在糖尿病发病后的6周和12周期间对小鼠进行研究。使用无创TonoLab眼压计测量眼压。在糖尿病诱导后的两个不同时间点对视网膜神经节细胞(RGCs)进行计数,并采用免疫荧光技术和定量分析进行检测。

结果

与年龄匹配的对照小鼠相比,糖尿病小鼠在糖尿病发病后的6周和12周时眼压水平显著升高(分别为p<0.01和p<0.001)。腹腔注射链脲佐菌素诱导的Brn3a+RGC和神经元细胞核+RGC(NeuN+RGC)丢失的时间进程遵循相似趋势。在糖尿病发病后的6周和12周,糖尿病小鼠中Brn3a+RGCs的数量(6周时p<0.05;12周时p<0.001)和NeuN+RGCs的数量(6周时p<0.05;12周时p<0.001)显著低于年龄匹配的对照小鼠。在视网膜平铺标本中,糖尿病小鼠中Brn3a+RGCs的数量(6周时p<0.05,12周时p<0.01)也显著低于对照小鼠。糖尿病小鼠的眼压与横切面上的RGCs呈负相关。糖尿病的眼压临界值为14.2 mmHg。

结论

这是一项关于糖尿病期间视网膜神经细胞丢失的特异性定量研究。这些数据表明糖尿病小鼠中发生了视网膜神经细胞减少。这表明RGC丢失可能是糖尿病视网膜病变的一个重要组成部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b02/3369894/3bc04ad5e532/mv-v18-1411-f1.jpg

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