Study of effects of antiglaucoma eye drops on N-methyl-D-aspartate-induced retinal damage
Study of effects of antiglaucoma eye drops on N-methyl-D-aspartate-induced retinal damage
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DOI：
10.1007/s10384-005-0253-5
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发表时间：
2005-11-01
影响因子：
2.4
通讯作者：
Nakazawa, M
中科院分区：
文献类型：
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作者：
Metoki, T;Ohguro, H;Nakazawa, M
目的：研究抗青光眼滴眼液对N-甲基-D-天冬氨酸(NMDA)诱导的大鼠视网膜损伤的影响。方法：应用多种抗青光眼滴眼液、β-受体阻滞剂、α/β受体阻滞剂、α1受体阻滞剂、α2受体激动剂和前列腺素衍生物，每天给NMDA大鼠滴眼2周，观察视网膜厚度、逆行标记的视网膜神经节细胞(RGC)数量和基因芯片分析结果。结果：NMDA玻璃体腔内给药后视网膜各层厚度明显减少，胶质纤维酸性蛋白(GFAP)表达上调。局部应用β-受体阻滞剂(噻吗洛尔、倍他洛尔和卡替洛尔)和前列腺素衍生物(拉坦前列素)对视网膜厚度、RGC数量或GFAR表达几乎没有显著影响。相比之下，α/β受体阻滞剂(尼普拉地洛和左丁洛尔)、α1受体阻滞剂(盐酸布纳洛尔)和α2受体激动剂(布莫尼定)对视网膜厚度和RGC数量有保护作用，并显著抑制NMDA诱导的GFAP上调。在与细胞调控机制相关的1101个基因中，胰岛素样生长因子(IGF-1)和ErbB3两个基因的表达在给予α/β受体阻滞剂、α1阻滞剂和α2激动剂后发生了变化。结论：抗青光眼滴眼液对α肾上腺素能受体α1阻断和α2刺激的调节可能对NMDA诱导的大鼠视网膜损伤有一定的保护作用。
Purpose: To study the effects of antiglaucoma eye drops on N-methyl-D-aspartate (NMDA)-induced retinal damage.Methods: Several antiglaucoma eye drops, beta-blockers, alpha/beta-blockers, an alpha 1-blocker, an alpha 2-agonist, and a prostaglandin derivative, were topically administrated to NMDA-treated rat eyes daily for 2 weeks, and the retinal thickness, the number of retrograde-labeled retinal ganglion cells (RGCs), and the results of a cDNA microarray analysis were studied.Results: Intravitreal administration of NMDA caused a significant decrease in the thickness of the retinal layers and induced upregulation of glial fibrillary acidic protein (GFAP). Topical administration of beta-blockers (timolol, betaxolol, and carteolol) and a prostaglandin derivative (latanoprost) showed almost no significant effects on retinal thickness, the number of RGCs, or expression of GFAR In contrast, the alpha/beta-blockers (nipradilol and levobunolol), the alpha 1-blocker (bunazosin HCl), and the alpha 2-agonist (brimonidine) showed preservation effects on retinal thickness and the number of RGCs, and marked suppression of NMDA-induced upregulation of GFAP. Among 1101 genes related to cellular regulatory mechanisms, the expression of two genes, both for insulin-like growth factors, (IGF-1) and ErbB3, was altered upon administration of the alpha/beta-blockers, the alpha 1-blocker, and the alpha 2-agonist.Conclusion: Our present study suggests that modulations of the a-adrenergic receptor, alpha 1-blocking and alpha 2-stimulation, by antiglaucoma eye drops may cause beneficial effects on NMDA-induced retinal damage in the rat.