Neuroprotective effects of angiotensin II type 1 receptor blocker in a rat model of chronic glaucoma.
Neuroprotective effects of angiotensin II type 1 receptor blocker in a rat model of chronic glaucoma.
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DOI：
10.1167/iovs.09-3678
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发表时间：
2009-12
影响因子：
4.4
通讯作者：
Hongwei Yang;K. Hirooka;Kouki Fukuda;F. Shiraga
中科院分区：
文献类型：
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作者：
Hongwei Yang;K. Hirooka;Kouki Fukuda;F. Shiraga
目的探讨血管紧张素Ⅱ 1型受体（AT 1-R）阻断剂坎地沙坦对青光眼动物模型视网膜神经节细胞（RGCs）神经毒性的保护作用。方法采用烧灼大鼠三条上巩膜血管的方法，造成一只眼慢性高眼压。然后用坎地沙坦（1 mg/kg/d）经口给药大鼠。在10周时，免疫组织化学用于定量RGC存活和检查AT 1-R的视网膜定位。结果与对侧对照眼相比，在实验期间，眼压持续升高约2.5倍。在10周坎地沙坦治疗结束时，血压没有变化。与具有正常IOP的对侧对照眼相比，在具有慢性、升高的IOP的眼睛的中央视网膜中，RGC存活率在未治疗的动物中为46.5% +/- 19.4%（平均值+/- SD），在坎地沙坦治疗的动物中为84.2% +/- 4.9%（P < 0.05;非配对t检验）。在正常眼压大鼠视网膜中，视网膜血管呈AT 1-R阳性。在IOP升高10周后，视网膜的免疫组织化学分析表明，坎地沙坦治疗的大鼠中有许多AT 1-R阳性RGCs，而溶剂治疗的大鼠中有明显的AT 1-R降低。结论：在大鼠慢性青光眼模型中，使用坎地沙坦的连续药物治疗导致对RGC损失的显著神经保护。
PURPOSE To investigate the neuroprotective effect of candesartan, an angiotensin II type 1 receptor (AT1-R) blocker, against the neurotoxicity of the retinal ganglion cells (RGCs) in an animal model of glaucoma. METHODS Cauterization of three episcleral vessels in rats was used to create chronically elevated intraocular pressure (IOP) in one eye. Rats were then treated orally with candesartan (1 mg/kg/d). At 10 weeks, immunohistochemistry was used for quantification of RGC survival and examination of retinal localization of AT1-R. RESULTS Compared with the contralateral control eyes, there was a consistently elevated IOP of approximately 2.5-fold during the experimental period. At the end of the 10-week candesartan treatment, there were no changes noted for the blood pressure. Compared with the contralateral control eyes that had normal IOP, the RGC survival rate in the central retina of eyes with the chronic, elevated IOP was 46.5% +/- 19.4% (mean +/- SD) in the untreated animals and 84.2% +/- 4.9% in the candesartan-treated animals (P < 0.05; unpaired t-test). In the retina of the normal IOP rat eyes, retinal vessels were positive for AT1-R. After 10 weeks of IOP elevation, immunohistochemical analysis of the retina indicated there were many AT1-R-positive RGCs in the candesartan-treated rat, whereas there was an apparent AT1-R decrease in the vehicle-treated rats. CONCLUSIONS In the rat chronic glaucoma model, continuous pharmacologic treatment using candesartan results in significant neuroprotection against RGC loss.