Kern T S, Miller C M, Tang J, Du Y, Ball S L, Berti-Matera L
Case Western Reserve University, Center for Diabetes Research, Cleveland, OH 44106, USA.
Mol Vis. 2010 Aug 15;16:1629-39.
We compared three rat strains to determine if different strains develop early-stage diabetic retinopathy or sensory neuropathy at different rates.
Sprague Dawley, Lewis, and Wistar rats were made diabetic with streptozotocin. Diabetic and nondiabetic animals had retinal vascular pathology measured at eight months of diabetes. The number of cells in the retinal ganglion cell layer (GCL), retinal function (using electroretinography [ERG]), and retinal levels of inducible nitric oxide synthase (iNOS), cyclooxygenase2 (COX2), and vascular endothelial growth factor (VEGF) were measured at four months of diabetes. Tactile allodynia was assessed in hind paws at two months of diabetes.
Diabetes of eight months' duration resulted in a significant increase in retinal degenerate capillaries and pericyte ghosts in Lewis and Wistar rats, but not in Sprague Dawley rats. A significant loss of cells in the GCL occurred only in diabetic Lewis rats, whereas Wistar and Sprague Dawley rats showed little change. Diabetes-induced iNOS and VEGF were statistically significant in all strains. Cyclooxygenase 2 (COX2) was significantly elevated in the Sprague Dawley and Wistar strains. Lewis rats showed a similar trend, however, the results were not statistically significant. All strains tended to show diabetes-induced impairment of dark-adapted b-wave amplitude, but only Sprague Dawley and Lewis strains had a significant reduction in latency. All strains showed significant tactile allodynia in peripheral nerves.
At the durations studied, Lewis rats showed accelerated loss of both retinal capillaries and ganglion cells in diabetes, whereas diabetic Wistar rats showed degeneration of the capillaries without significant neurodegeneration, and Sprague Dawley rats showed neither lesion. Identification of strains that develop retinal lesions at different rates should be of value in investigating the pathogenesis of retinopathy.
我们比较了三种大鼠品系，以确定不同品系是否以不同速率发展为早期糖尿病视网膜病变或感觉神经病变。
用链脲佐菌素使斯普拉格·道利大鼠、刘易斯大鼠和威斯塔大鼠患糖尿病。糖尿病和非糖尿病动物在糖尿病8个月时测量视网膜血管病理。在糖尿病4个月时测量视网膜神经节细胞层（GCL）中的细胞数量、视网膜功能（使用视网膜电图[ERG]）以及诱导型一氧化氮合酶（iNOS）、环氧化酶2（COX2）和血管内皮生长因子（VEGF）的视网膜水平。在糖尿病2个月时评估后爪的触觉异常性疼痛。
病程8个月的糖尿病导致刘易斯大鼠和威斯塔大鼠的视网膜退化毛细血管和周细胞鬼影显著增加，但斯普拉格·道利大鼠没有。仅糖尿病刘易斯大鼠的GCL中细胞显著丢失，而威斯塔大鼠和斯普拉格·道利大鼠变化不大。糖尿病诱导的iNOS和VEGF在所有品系中均有统计学意义。环氧化酶2（COX2）在斯普拉格·道利品系和威斯塔品系中显著升高。刘易斯大鼠呈现类似趋势，然而，结果无统计学意义。所有品系均倾向于表现出糖尿病诱导的暗适应b波振幅受损，但只有斯普拉格·道利品系和刘易斯品系的潜伏期显著缩短。所有品系在外周神经中均表现出显著的触觉异常性疼痛。
在所研究的病程中，刘易斯大鼠在糖尿病中视网膜毛细血管和神经节细胞的丢失加速，而糖尿病威斯塔大鼠表现出毛细血管退化但无明显神经变性，斯普拉格·道利大鼠则未出现病变。鉴定以不同速率发展视网膜病变的品系对于研究视网膜病变的发病机制应具有重要价值。
