Oxidative deoxyribonucleic acid damage in the eyes of glaucoma patients
Oxidative deoxyribonucleic acid damage in the eyes of glaucoma patients
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DOI：
10.1016/s0002-9343(03)00114-1
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发表时间：
2003-06-01
影响因子：
5.9
通讯作者：
De Flora, S
中科院分区：
文献类型：
--
作者：
Izzotti, A;Saccà, SC;De Flora, S
背景：青光眼是世界范围内不可逆性失明的主要原因，青光眼发生的分子机制知之甚少。一些研究人员推测，这可能与氧化损伤有关。以8-羟基-2‘-脱氧鸟苷(8-OH-DG)为指标，对42例青光眼患者和45例年龄、性别相近的青光眼患者小梁网区8-OH-DG水平进行了检测。结果：青光眼患者血浆8-OH-DG水平明显高于正常对照组。青光眼患者的DNA氧化损伤与眼压显著相关；在原发性开角型青光眼患者中，氧化DNA损伤也与视野缺陷相关。GSTT1在两组中相似，但对8-OH-DG水平无影响。相反，GSTM1缺失者的8-OH-DG水平显著高于GSTM1阳性者。结论：青光眼患者小梁细胞DNA氧化损伤明显增加，GSTM1基因缺失在青光眼患者小梁细胞中的表达明显增加。GSTM1基因缺失与动脉粥样硬化中不同部位癌症和分子损害的风险增加有关，容易导致青光眼患者更严重的DNA氧化损伤。这些发现可能有助于了解青光眼的发病机制，并可能对青光眼的预防和治疗有所帮助。(C)2003年，由Excerpta Medica Inc.
BACKGROUND: Little is known about the molecular mechanisms responsible for the development of glaucoma, the leading cause of irreversible blindness worldwide. Some investigators have hypothesized that oxidative damage may be involved. We evaluated oxidative deoxyribonucleic acid (DNA) damage, in terms of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), in the eyes of glaucoma patients.METHODS: Levels of 8-OH-dG were measured in the trabecular meshwork region from 42 patients with glaucoma and 45 controls of similar age and sex. Genotypes of glutathione S-transferase isoenzymes (GSTM1 and GSTT1) were assessed by polymerase chain reaction in the same DNA samples.RESULTS: Levels of 8-OH-dG were significantly higher in glaucoma patients than in controls. Oxidative DNA damage in patients with glaucoma correlated significantly with intraocular pressure; in patients with primary open-angle glaucoma, it also correlated with visual field defects. GSTT1 was similar in the two groups, and had no effect on 8-OH-dG levels. Conversely, 8-OH-dG levels were significantly higher in GSTM1-null than in GSTM1-positive subjects. The GSTM1-null genotype was significantly more common in patients with primary open-angle glaucoma than in controls.CONCLUSION: Oxidative DNA damage is significantly increased in the trabecular meshwork of glaucoma patients. GSTM1 gene deletion, which has been associated with an increased risk of cancer at various sites and molecular lesions in atherosclerosis, predisposes to more severe oxidative DNA damage in glaucoma patients. These findings may contribute to understanding the pathogenesis of glaucoma and maybe useful in the prevention and treatment of this disease. (C) 2003 by Excerpta Medica Inc.