Nicotinamide attenuates retinal ischemia and light insults to neurones
Nicotinamide attenuates retinal ischemia and light insults to neurones
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DOI：
10.1016/j.neuint.2007.09.012
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发表时间：
2008-03-01
影响因子：
4.2
通讯作者：
Osborne, Neville N.
中科院分区：
文献类型：
--
作者：
Ji, Dan;Li, Guang-Yu;Osborne, Neville N.
本研究的目的是确定烟酰胺是否能有效地减弱缺血/再灌注对大鼠视网膜原位和光对培养的转化视网膜神经节细胞（RGC-5细胞）的负面影响。就在缺血前腹膜内给予烟酰胺，并在损伤后立即给予玻璃体。记录缺血前及缺血后5天双眼视网膜电图（ERG）。缺血后7天，分析视网膜的各种抗原的定位。还制备视网膜和视神经提取物用于分析特定蛋白质和mRNA。此外，给予培养物中的RGC-5细胞光损伤（1000勒克斯，48和96小时），并通过各种程序确定活力降低和凋亡的证据。将烟酰胺加入到一些培养物中以观察其是否逆转了光的负面效应。视网膜缺血/再灌注影响Thy-1、神经元型一氧化氮合酶（NOS）和胆碱乙酰转移酶（ChAT）的定位、ERG的a波和b波振幅、各种视网膜和视神经蛋白和mRNA的含量。值得注意的是，烟酰胺在统计学上减弱了缺血/再灌注诱导的许多效应，包括聚ADP-核糖聚合酶（PARP）的激活。烟酰胺和PARP抑制剂NU 1025可减弱光诱导的培养RGC-5细胞凋亡。所提供的数据表明，烟酰胺可分别减轻缺血/再灌注和光引起的培养视网膜和RGC-5细胞的损伤。有证据表明，烟酰胺作为PARP抑制剂，并可能是一种抗氧化剂。(C)2007爱思唯尔有限公司保留所有权利。
The aim of the present studies was to determine whether nicotinamide is effective in blunting the negative influence of ischemia/reperfusion to the rat retina in situ and of light to transformed retinal ganglion cells (RGC-5 cells) in culture.Ischemia was delivered to the retina of one eye of rats by raising the intraocular pressure. Nicotinamide was administered intraperitoneally just before ischemia and into the vitreous immediately after the insult. Electroretinograms (ERGs) of both eyes were recorded before and 5 days after ischemia. Seven days after ischemia, retinas were analysed for the localization of various antigens. Retinal and optic nerve extracts were also prepared for analysis of specific proteins and mRNAs. Also, RGC-5 cells in culture were given a light insult (1000 lux, 48 and 96 h) and evidence for reduced viability and apoptosis determined by a variety of procedures. Nicotinamide was added to some cultures to see whether it reversed the negative effect of light.Ischemia/reperfusion to the retina affected the localization of Thy-1, neuronal nitric oxide synthase (NOS) and choline acetyltransferase (ChAT), the a- and b-wave amplitudes of the ERG, the content of various retinal and optic nerve proteins and mRNAs. Significantly, nicotinamide statistically blunted many of the effects induced by ischemia/reperfusion which included the activation of poly-ADP-ribose polymerase (PARP). Light-induced apoptosis of RGC-5 cells in culture was attenuated by nicotinamide and the PARP inhibitor NU1025.The presented data show that nicotinamide attenuates injury to the retina and RGC-5 cells in culture caused by ischemia/reperfusion and by light, respectively. Evidence is provided to suggest that nicotinamide acts as a PARP inhibitor and possibly an antioxidant. (C) 2007 Elsevier Ltd. All rights reserved.