Akt is activated via insulin/IGF-1 receptor in rat retina with episcleral vein cauterization
Akt is activated via insulin/IGF-1 receptor in rat retina with episcleral vein cauterization
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DOI：
10.1016/j.brainres.2004.06.077
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发表时间：
2004-10-01
期刊：
影响因子：
2.9
通讯作者：
Negi, A
中科院分区：
文献类型：
--
作者：
Kanamori, A;Nakamura, M;Negi, A
Akt 丝氨酸/苏氨酸激酶介导视网膜中的促生存信号传导，据报道在某些视网膜和视神经损伤的反应中被激活。人类和实验性青光眼会诱导视网膜神经节细胞 (RGC) 凋亡。本研究的目的是测试通过外巩膜静脉烧灼 (EVC) 来长期升高大鼠眼压 (IOP) 是否会增加 RGC 的凋亡并影响 Akt 及其上游胰岛素样生长因子 (IGF)-1 受体/胰岛素受体的激活。烧灼 Sprague-Dawley 大鼠左眼的三根巩膜外静脉以升高 IOP。长达 6 个月的时间里，我们对眼压进行监测，并在几个时间点解剖视网膜。计数平装视网膜中末端 dUTP 缺口末端标记 (TUNEL) 阳性细胞的数量和荧光金标记的 RGC 的数量。进行免疫组织化学和免疫印迹来鉴定表达磷酸化 Akt 的细胞并量化 Akt 和 IGF-1 受体/胰岛素受体的磷酸化与总比率。 EVC 在 2 个月内显着提高 ION，以 IOP 依赖性方式增加 TUNEL 阳性细胞，并在 6 个月时减少 34.5% 的 RGC（P
The Akt serine/threonine kinase mediates pro-survival signalings in retina and was reported to be activated in a response to some retinal and optic nerve injuries. Human and experimental glaucoma induce apoptosis of retinal ganglion cells (RGCs). The purpose of this study is to test whether episcleral vein cauterization (EVC) to chronically elevate intraocular pressures (IOPs) in rats increase apoptosis of RGCs and affect activation of Akt and its upstream insulin-like growth factor (IGF)-1 receptor/Insulin receptor. Three episcleral veins in left eyes of Sprague-Dawley rats were cauterized to elevate IOPs. Up to 6 months, IOPs were monitored and the retina was dissected at several time points. The numbers of terminal dUTP nick end labeling (TUNEL)-positive cells and those of RGCs labeled with fluorogold were counted in flat-mounted retina. Immunohistochemistry and immunoblotting were performed to identify cells expressing phosphorylated Akt and to quantify the phospho- to total ratios of Akt and IGF-1 receptor/insulin receptor. EVC significantly elevated ION up to 2 months, increased TUNEL-positive cells in an IOP-dependent fashion, and reduced 34.5% of RGCs at 6 months (P