Systemic administration of nilvadipine delays photoreceptor degeneration of heterozygous retinal degeneration slow (rds) mouse
Systemic administration of nilvadipine delays photoreceptor degeneration of heterozygous retinal degeneration slow (rds) mouse
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DOI：
10.1016/j.exer.2007.09.008
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发表时间：
2008-01-01
影响因子：
3.4
通讯作者：
Mizukoshi, Sayuri
中科院分区：
文献类型：
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作者：
Takeuchi, Kimio;Nakazawa, Mitsuru;Mizukoshi, Sayuri
为了研究钙通道阻滞剂尼伐地平对视网膜变性慢（rds）小鼠视网膜的影响，我们将尼伐地平腹腔注射到杂合rds小鼠体内长达200天。采用视网膜电图（ERG）、光镜和电镜、DNA芯片、定量逆转录酶聚合酶链反应（RT-PCR）和western-blot分析评价尼伐地平的疗效。尼伐地平治疗后ERG a波、b波均显著高于对照组（p < 0.01）。尽管尼伐地平治疗组和对照组在光镜下的组织学发现没有差异，但在电子显微镜下，治疗组明显保存了光感受器盘。与对照组相比，治疗组视紫红质水平也有所升高。DNA微阵列分析发现，编码蛋白质合成、生长因子和神经营养因子(如纤毛神经营养因子（CNTF）和成纤维细胞生长因子（FGFs22和13）的基因表达增加。蛋白水解、凋亡和生长因子（FGF18）相关蛋白编码基因的表达也有所下降。定量RT-PCR和western-blot分析均证实CNTF FGF22和FGF13表达升高，FGF18表达降低。此外，FGF2在治疗组和对照组均有组成性表达。由于已知CNTF可以延缓rds小鼠或其他遗传性视网膜变性模型的视网膜变性，因此尼伐地平对rds视网膜变性具有光受体存活作用，部分原因可能是通过增强视网膜中内源性CNTF的表达。(C) 2007 Elsevier Ltd.版权所有。
To investigate the effect of nilvadipine, a calcium channel blocker, upon the retina of retinal degeneration slow (rds) mouse, nilvadipine was intraperitoneally injected into heterozygous rds mice for up to 200 days. The effect of nilvadipine was evaluated by electroretinography (ERG), light and electron microscopies, DNA microarray, quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and western-blot analysis. After nilvadipine treatment, both a- and b-waves of ERG were significantly higher than in the control group (p < 0.01). Although there was no difference in histological findings by light microscopy between the nilvadipine treated group and control group, apparent preservation of photoreceptor disc was demonstrated by electron microscopy in the treated group. Rhodopsin level was also increased in the treated group comparing to the control group. The DNA microarray analysis detected increased expression of genes encoding proteins which function in protein synthesis, growth factors and neurotrophic factor like ciliary neurotrophic factor (CNTF) and fibroblast growth factors (FGFs22 and 13). Decreased expression of genes coding for proteins related to proteolysis, apoptosis and growth factor (FGF18) was also demonstrated. Increased expression of CNTF FGF22 and FGF13 and decreased expression of FGF18 were confirmed by both quantitative RT-PCR and western-blot analysis. In addition, FGF2 was constitutively expressed in both treated and control groups. Since CNTF has been known to retard retinal degeneration by rds mouse or other models of inherited retinal degeneration, it is possible that nilvadipine has a photoreceptor survival effect on rds retinal degeneration partly by enhancing expression of endogenous CNTF in the retina. (C) 2007 Elsevier Ltd. All rights reserved.