Study of drug effects of calcium channel blockers on retinal degeneration of rd mouse
Study of drug effects of calcium channel blockers on retinal degeneration of rd mouse
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DOI：
10.1016/j.bbrc.2003.12.034
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发表时间：
2004-01-23
影响因子：
3.1
通讯作者：
Nakazawa, M
中科院分区：
文献类型：
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作者：
Takano, Y;Ohguro, H;Nakazawa, M
本研究通过观察钙离子拮抗剂对rd小鼠视网膜变性的影响，评价其疗效。腹腔注射地尔硫卓、尼卡地平、尼伐地平和硝苯地平等钙离子拮抗剂后，观察视网膜形态和功能。此外，我们在尼伐地平治疗和对照视网膜中进行了DNA微阵列分析，以了解它们在分子水平上的药物作用。我们发现尼伐地平在rd小鼠视网膜变性的初始阶段能显著地保护视网膜厚度，尼卡地平也表现出明显的保护作用，但不如尼伐地平。然而，我们认为没有保存效果的地尔硫卓和硝苯地平。在总共3774个基因中，27个基因的表达在给予尼伐地平后发生改变，包括与凋亡途径、神经存活因子、Ca 2+代谢和其他机制相关的几个基因。提示尼伐地平、尼卡地平等钙通道阻滞剂对视网膜光感受器细胞有保护作用，可用于治疗某些视网膜病变。(C)2003年爱思唯尔公司All rights reserved.
In the present study, we studied drug effects of Ca2+ antagonists on the retinal degeneration of rd mouse to evaluate their efficacy. Several kinds of Ca2+ antagonists, diltiazem, nicardipine, nilvadipine or nifedipine were administrated intraperitoneally and thereafter retinal morphology and functions were analyzed. In addition, we performed DNA microarray analysis both in nilvadipine treated and control retinas to understand their drug effects at molecular levels. We found that nilvadipine caused significant preservation of retinal thickness in rd mouse during the initial stage of the retinal degeneration, and nicardipine showed also significant but lesser preservation than nilvadipine. However, we recognized no preservation effects of diltiazem and nifedipine. In the total 3774 genes, the expressions of 27 genes were altered upon administration of nilvadipine, including several genes related to the apoptotic pathway, neuro-survival factor, Ca2+ metabolisms, and other mechanisms. It is suggested that some types of Ca2+ channel blockers, such as nilvadipine and nicardipine, are able to preserve photoreceptor cells in rd mouse and can potentially be used to treat some RP patients. (C) 2003 Elsevier Inc. All rights reserved.