Death of retinal neurons in streptozotocin-induced diabetic mice
Death of retinal neurons in streptozotocin-induced diabetic mice
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DOI：
10.1167/iovs.04-0247
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Smith, SB
中科院分区：
文献类型：
--
作者：
Martin, PM;Roon, P;Smith, SB
目的.在患有糖尿病视网膜病变的人的视网膜和糖尿病大鼠模型中已经报道了神经元细胞死亡。关于糖尿病视网膜病变小鼠模型中的神经元细胞死亡知之甚少。本研究旨在确定糖尿病小鼠视网膜神经元是否丢失以及这种丢失是否涉及凋亡过程。用链脲佐菌素使三周龄的C57 B1/6小鼠患糖尿病。他们在糖尿病发作后的14周内进行了研究。对眼睛进行形态学分析，并通过TUNEL分析和活化的caspase-3检测凋亡细胞，并进行电子显微镜检查。对糖尿病14周小鼠视网膜横截面的形态测量分析显示，与年龄匹配的对照小鼠相比，神经节细胞层中的细胞减少了20%至25%。在糖尿病10周的小鼠中，整个视网膜以及内核层和外核层的厚度有适度但显著的减少。TUNEL分析和活性caspase-3的检测显示，神经节细胞层的细胞凋亡死亡。电镜下可见神经节细胞层细胞核圆齿状核、染色质边集等凋亡特征。这些数据表明，在糖尿病小鼠视网膜中，神经节细胞层中的神经元死亡，并且这种死亡通过凋亡途径发生。糖尿病小鼠可能是研究糖尿病神经细胞死亡的合适和有价值的模型。
PURPOSE. Neuronal cell death has been reported in retinas of humans with diabetic retinopathy and in diabetic rat models. Little is known about neuronal cell death in mouse models of diabetic retinopathy. This study was designed to determine whether neurons are lost in diabetic mouse retinas and whether the loss involves an apoptotic process.METHODS. Three-week-old C57Bl/6 mice were made diabetic with streptozotocin. They were studied over the course of 14 weeks after onset of diabetes. Eyes were processed for morphometric analysis and detection of apoptotic cells by TUNEL analysis and activated caspase-3 and were subjected to electron microscopy.RESULTS. Morphometric analysis of retinal cross sections of mice that had been diabetic 14 weeks showed similar to 20% to 25% fewer cells in the ganglion cell layer compared with age-matched control mice. There was a modest, but significant, decrease in the thickness of the whole retina and the inner and outer nuclear layers in mice that had been diabetic for 10 weeks. TUNEL analysis and detection of active caspase-3 revealed that cells of the ganglion cell layer were dying by apoptosis. Electron microscopic analysis detected morphologic features characteristic of apoptosis, including margination of chromatin and crenated nuclei of cells in the ganglion cell layer.CONCLUSIONS. The data suggest that in diabetic mouse retinas, neurons in the ganglion cell layer die, and this death occurs through an apoptotic pathway. Diabetic mice may be appropriate and valuable models for studies of neuronal cell death in diabetes.