Retinal degeneration from oxidative damage

Retinal degeneration from oxidative damage
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DOI:
10.1016/j.freeradbiomed.2005.09.032
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发表时间:
2006-02-15
影响因子:
7.4
通讯作者:
Campochiaro, PA
Campochiaro, PA
中科院分区:
医学1区
文献类型:
--
作者:
Cingolani, C;Rogers, B;Campochiaro, PA

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百草枯是一种产生活性氧的除草剂,已被用于探测肺的氧化防御系统。在本研究中,我们研究了百草枯对视网膜的影响。C57BL/6小鼠玻璃体内注射1 μ l 0.5 mM百草枯后,视网膜电图(ERG) a波和b波振幅无明显下降,但注射0.75或1 mM百草枯后,ERG功能丧失。在注射百草枯的眼睛中,组织学显示染色质凝结,内外核层变薄,表明细胞死亡,末端脱氧核苷酸转移酶介导的dutp -生物素末端标记表明细胞死亡的机制之一是凋亡。眼内注射百草枯后再灌注氢乙胺后,视网膜和视网膜色素上皮的荧光显示高水平的超氧自由基,丙烯醛染色和羰基加合物酶联免疫吸附试验显示氧化损伤。BALB/c小鼠与C57BL/6小鼠相比,百草枯引起的外核层损伤更大,这表明光感受器和/或其他修饰基因的氧化防御系统存在品系差异。玻璃体内注射百草枯提供了一种氧化损伤性视网膜变性的新模型,可能有助于测试新的抗氧化治疗方法。(c) 2005爱思唯尔公司版权所有。
Paraquat, a herbicide that generates reactive oxygen species, has been used to probe the oxidative defense systems of lung. In this study, we investigated the effects of paraquat in the retina. There was no significant decline in electroretinogram, (ERG) a- or b-wave amplitudes after intravitreous injection of 1 mu l of 0.5 mM paraquat in C57BL/6 mice, but loss of ERG function occurred after injection of 0.75 or 1 mM paraquat. Histology in paraquat-injected eyes showed condensation of chromatin and thinning of the inner and outer nuclear layers indicating cell death, and terminal deoxynucleotidyl transferase-mediated duTP-biotinide end labeling demonstrated that one mechanism of cell death was apoptosis. Fluorescence in the retina and retina] pigmented epithelium after intraocular injection of paraquat followed by perfusion with hydroethidine indicated high levels of superoxide radicals, and oxidative damage was demonstrated by staining for acrolein and enzyme-linked immunosorbent assay for carbonyl adducts. Paraquat-induced damage to the outer nuclear layer was greater in BALB/c mice than in C57BL/6 mice, suggesting strain differences in the oxidative defense system of photoreceptors and/or other modifier genes. Intravitreous injection of paraquat provides a new model of oxidative damage-induced retinal degeneration that is likely to be useful for testing new antioxidant treatments. (c) 2005 Elsevier Inc. All rights reserved.