Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
CNS Neurosci Ther. 2013 Dec;19(12):945-53. doi: 10.1111/cns.12150. Epub 2013 Jul 22.
Dysfunction of glutamate uptake, largely mediated by the glutamate-aspartate transporter (GLAST), may lead to retinal cell apoptosis in diabetic retinopathy. The aim of this study is to examine how cell apoptosis and the expression level of GLAST in neural retina of a diabetic rat model are changed and whether the neuroretinal apoptosis could be ameliorated by the administration of glial cell line-derived neurotrophic factor (GDNF).
Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) in Sprague-Dawley rats. GLAST protein expression levels were determined by Western blotting, whereas apoptosis of retinal neurons was evaluated by TUNEL staining. To assess the role of GDNF in ameliorating the STZ-induced retinal changes, GDNF/GDNF with siRNA directed against GLAST was injected into the vitreous after STZ injection.
In rat retinas 4 weeks after the onset of STZ-induced diabetes, TUNEL-positive cells were significantly increased, whereas GLAST levels were significantly reduced. Intraocular administration of GDNF at the early stage of diabetes remarkably increased the GLAST levels and decreased TUNEL-positive signals in the retinas. These effects of GDNF were largely abolished by coadministration of GLAST siRNA.
GDNF, administrated at the early stage of diabetes, could rescue retinal cells from neurodegeneration by upregulating the expression of GLAST.
谷氨酸摄取功能障碍，主要由谷氨酸-天冬氨酸转运体（GLAST）介导，可能导致糖尿病视网膜病变中的视网膜细胞凋亡。本研究旨在探讨糖尿病大鼠模型中神经视网膜细胞凋亡和 GLAST 表达水平的变化，以及胶质细胞系衍生的神经营养因子（GDNF）是否能改善神经视网膜凋亡。
链脲佐菌素（STZ）腹腔注射诱导 Sprague-Dawley 大鼠糖尿病。通过 Western blot 测定 GLAST 蛋白表达水平，通过 TUNEL 染色评估视网膜神经元凋亡。为了评估 GDNF 在改善 STZ 诱导的视网膜变化中的作用，在 STZ 注射后将 GDNF/GDNF 与针对 GLAST 的 siRNA 注入玻璃体内。
在 STZ 诱导糖尿病发生后 4 周，大鼠视网膜中 TUNEL 阳性细胞明显增加，而 GLAST 水平明显降低。糖尿病早期眼内给予 GDNF 可显著增加 GLAST 水平，并减少视网膜中 TUNEL 阳性信号。GLAST siRNA 的共给予大大消除了 GDNF 的这些作用。
糖尿病早期给予 GDNF 可通过上调 GLAST 的表达来挽救视网膜细胞的神经退行性变。
