An electrophysiological study of retinal function in the diabetic female rat

An electrophysiological study of retinal function in the diabetic female rat
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DOI:
10.1167/iovs.06-0364
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发表时间:
2006-11-01
影响因子:
4.4
通讯作者:
Qian, Haohua
Qian, Haohua
中科院分区:
医学2区
文献类型:
--
作者:
Ramsey, David J.;Ripps, Harris;Qian, Haohua

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目的.观察链脲佐菌素(STZ)诱导的糖尿病雌性Long-Evans大鼠视网膜功能。通过静脉注射STZ诱导高血压,并在12周内以4周的间隔记录ERG反应。振荡电位(OP)和间歇性刺激的反应进行了分析与定制的计算机程序。用膜片钳记录单个视杆双极细胞的GABA诱导反应,并用免疫组织化学方法说明GABA(γ-氨基丁酸)和GABA C受体的视网膜分布。在注射STZ后2至3天,大鼠出现高血压。与先前关于糖尿病对雄性大鼠影响的报道相比,STZ治疗的雌性大鼠的视觉功能异常似乎较轻。糖尿病和对照动物之间的ERG的a-或b-波分量的灵敏度或振幅没有观察到显着差异,两个动物组表现出类似的神经元暗适应的时间过程。与此相反,糖尿病动物表现出显着差异的模式的OP和他们的响应闪烁的幅度。GABA在糖尿病大鼠视网膜内层的积累,结合单个双极细胞的膜片钳记录结果,揭示了近端视网膜GABA信号的潜在回路受到高血糖的影响。结果表明,GABA信号通路的变化可能是STZ诱导的糖尿病大鼠ERG反应改变的潜在细胞机制。认识到这些早期神经感觉缺陷将使我们能够更好地了解糖尿病视网膜病变的病理生理基础。
PURPOSE. To examine retinal function in female Long-Evans rats with streptozotocin (STZ)-induced diabetes.METHODS. Hyperglycemia was induced by IV injection of STZ, and ERG responses were recorded at 4-week intervals over 12 weeks. Oscillatory potentials (OPs) and responses to intermittent stimulation were analyzed with a custom computer program. The GABA-induced responses of individual rod bipolar cells were obtained from patch-clamp recordings, and immunohistochemistry was used to illustrate the retinal distribution of GABA (gamma-aminobutyric acid) and GABA C receptors.RESULTS. Hyperglycemia developed in rats 2 to 3 days after injection of STZ. Compared with previous reports of the effects of diabetes in male rats, visual function abnormalities appeared to be milder in STZ-treated female rats. No significant differences were observed in the sensitivity or amplitude of the a- or b-wave components of the ERG between diabetic and control animals, and both animal groups exhibited a similar time course of neuronal dark adaptation. In contrast, diabetic animals showed significant differences in the pattern of OPs and in the amplitudes of their responses to flicker. The accumulation of GABA in the inner retina of diabetic rats, combined with the results of patch-clamp recordings from individual bipolar cells, revealed that the circuitry underlying the GABA signal of the proximal retina is affected by hyperglycemia.CONCLUSIONS. The results suggest that changes in the GABA-signaling pathway may be the underlying cellular mechanism for altered ERG responses in STZ-induced diabetes in rats. Recognition of these early neurosensory defects would enable a better understanding of the pathophysiological basis of diabetic retinopathy.