Retinal glutamate transporter changes in experimental glaucoma and after optic nerve transection in the rat.
Retinal glutamate transporter changes in experimental glaucoma and after optic nerve transection in the rat.
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发表时间：
2002-07
影响因子：
4.4
通讯作者：
Keith R G Martin;H. Levkovitch-Verbin;Danielle F Valenta;Lisa A. Baumrind;M. Pease;H. A. Quigley
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文献类型：
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作者：
Keith R G Martin;H. Levkovitch-Verbin;Danielle F Valenta;Lisa A. Baumrind;M. Pease;H. A. Quigley
目的：高水平的谷氨酸可能对视网膜神经节细胞有毒。因此，视网膜谷氨酸转运体对细胞外谷氨酸的有效缓冲是重要的。本研究旨在探讨两种视神经损伤模型大鼠的谷氨酸转运体是否发生改变。方法采用经角膜缘二极管激光治疗成年Wistar大鼠单眼青光眼。另外25只大鼠进行单侧视神经横断。采用免疫组织化学和定量Western blot方法研究谷氨酸转运体GLAST （EAAT-1）和GLT-1 （EAAT-2）。伤后第3天、第1、4、6周比较治疗组和对照组。在环氧树脂包埋的视神经横截面上半定量评估视神经损伤。结果所有动物小梁激光治疗后眼压均有中度升高。实验青光眼1 ~ 6周后，所有治疗过的眼睛都有明显的视神经损伤。免疫组化未检测谷氨酸转运蛋白的变化。Western blot分析显示，与对照组相比，青光眼GLT-1在第3天（29.3% +/- 6.7%,P = 0.01）、第1周（55.5% +/- 13.6%,P = 0.02）、第4周（27.2% +/- 10.1%,P = 0.05）和第6周（38.1% +/- 7.9%,P = 0.01）显著降低；平均降低+/- SEM，配对t检验，每组n = 5只动物，每只眼睛4次重复Western blot分析。GLT-1的降低幅度与青光眼的平均IOP有显著相关性（r(2) = 0.31, P = 0.01，线性回归）。IOP升高4周后，GLAST显著降低（33.8% +/- 8.1%，平均+/- SEM） （P = 0.01，配对t检验，每组n = 5只）。与青光眼相比，视神经横断导致GLT-1较对照眼升高（P = 0.01，配对t检验，n = 15只动物）。横断后GLAST无明显变化。结论：GLT-1和GLAST在实验性大鼠青光眼模型中显著降低，而视神经横断后没有发现这种反应。GLT-1和GLAST的减少可能会增加青光眼中谷氨酸诱导的RGC损伤的可能性。
PURPOSE High levels of glutamate can be toxic to retinal ganglion cells. Effective buffering of extracellular glutamate by retinal glutamate transporters is therefore important. This study was conducted to investigate whether glutamate transporter changes occur with two models of optic nerve injury in the rat. METHODS Glaucoma was induced in one eye of 35 adult Wistar rats by translimbal diode laser treatment to the trabecular meshwork. Twenty-five more rats underwent unilateral optic nerve transection. Two glutamate transporters, GLAST (EAAT-1) and GLT-1 (EAAT-2), were studied by immunohistochemistry and quantitative Western blot analysis. Treated and control eyes were compared 3 days and 1, 4, and 6 weeks after injury. Optic nerve damage was assessed semiquantitatively in epoxy-embedded optic nerve cross sections. RESULTS Trabecular laser treatment resulted in moderate intraocular pressure (IOP) elevation in all animals. After 1 to 6 weeks of experimental glaucoma, all treated eyes had significant optic nerve damage. Glutamate transporter changes were not detected by immunohistochemistry. Western blot analysis demonstrated significantly reduced GLT-1 in glaucomatous eyes compared with control eyes at 3 days (29.3% +/- 6.7%, P = 0.01), 1 week (55.5% +/- 13.6%, P = 0.02), 4 weeks (27.2% +/- 10.1%, P = 0.05), and 6 weeks (38.1% +/- 7.9%, P = 0.01; mean reduction +/- SEM, paired t-tests, n = 5 animals per group, four duplicate Western blot analyses per eye). The magnitude of the reduction in GLT-1 correlated significantly with mean IOP in the glaucomatous eye (r(2) = 0.31, P = 0.01, linear regression). GLAST was significantly reduced (33.8% +/- 8.1%, mean +/- SEM) after 4 weeks of elevated IOP (P = 0.01, paired t-test, n = 5 animals per group). In contrast to glaucoma, optic nerve transection resulted in an increase in GLT-1 compared with the control eye (P = 0.01, paired t-test, n = 15 animals). There was no significant change in GLAST after transection. CONCLUSIONS GLT-1 and GLAST were significantly reduced in an experimental rat glaucoma model, a response that was not found after optic nerve transection. Reductions in GLT-1 and GLAST may increase the potential for glutamate-induced injury to RGC in glaucoma.