Ramsey David J, Ripps Harris, Qian Haohua
Departments of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, 1955 W. Taylor Street, Chicago, IL 60612, USA.
Invest Ophthalmol Vis Sci. 2006 Nov;47(11):5116-24. doi: 10.1167/iovs.06-0364.
To examine retinal function in female Long-Evans rats with streptozotocin (STZ)-induced diabetes.
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.
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.
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.
研究链脲佐菌素（STZ）诱导的糖尿病雌性Long-Evans大鼠的视网膜功能。
通过静脉注射STZ诱导高血糖，并在12周内每隔4周记录视网膜电图（ERG）反应。使用定制的计算机程序分析振荡电位（OPs）和对间歇性刺激的反应。从膜片钳记录中获得单个视杆双极细胞的γ-氨基丁酸（GABA）诱导反应，并使用免疫组织化学法显示GABA和GABA(C)受体在视网膜中的分布。
注射STZ后2至3天大鼠出现高血糖。与先前关于糖尿病对雄性大鼠影响的报道相比，STZ处理的雌性大鼠的视觉功能异常似乎较轻。糖尿病动物和对照动物之间，ERG的a波或b波成分的敏感性或振幅未观察到显著差异，且两组动物的神经元暗适应时间进程相似。相反，糖尿病动物在OPs模式及其对闪烁反应的振幅方面表现出显著差异。糖尿病大鼠内视网膜中GABA的积累，结合单个双极细胞的膜片钳记录结果，表明近端视网膜GABA信号传导的神经回路受高血糖影响。
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有助于更好地理解糖尿病视网膜病变的病理生理基础。
