Altered Antioxidant-Oxidant Status in the Aqueous Humor and Peripheral Blood of Patients with Retinitis Pigmentosa

Altered Antioxidant-Oxidant Status in the Aqueous Humor and Peripheral Blood of Patients with Retinitis Pigmentosa
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DOI:
10.1371/journal.pone.0074223
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发表时间:
2013-09-12
期刊:
影响因子:
3.7
通讯作者:
Rodrigo, Regina
Rodrigo, Regina
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Martinez-Fernandez de la Camara, Cristina;Salom, David;Rodrigo, Regina

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色素性视网膜炎是遗传性视网膜变性的一种常见形式,是发达国家失明的最大孟德尔遗传原因。人们普遍认为氧化应激可能参与其发病机制。我们测量了56名色素性视网膜炎患者和60名无系统性或眼部氧化应激相关疾病的受试者的总抗氧化能力、游离硝基酪氨酸、硫代巴比托酸反应性物质(TBARS)形成、细胞外超氧化物歧化酶(SOD3)活性、蛋白质、一氧化氮/环GMP途径代谢物、血红素加氧酶i和诱导型一氧化氮合酶表达水平。多变量协方差分析显示,视网膜色素变性改变了眼部抗氧化防御机制和血液中的氧化还原状态。色素性视网膜炎患者总体抗氧化能力较低,包括房水中SOD3活性和蛋白浓度降低。患者还表现出SOD3活性降低,TBARS形成增加,外周血一氧化氮/循环GMP通路上调。总之,这些发现证实了视网膜色素变性患者眼部抗氧化状态降低的假设。此外,这些患者外周血中一些氧化-亚硝化标志物出现变化。需要进一步的研究来阐明这些外周标志物与视网膜色素变性之间的关系。
Retinitis Pigmentosa is a common form of hereditary retinal degeneration constituting the largest Mendelian genetic cause of blindness in the developed world. It has been widely suggested that oxidative stress possibly contributes to its pathogenesis. We measured the levels of total antioxidant capacity, free nitrotyrosine, thiobarbituric acid reactive substances (TBARS) formation, extracellular superoxide dismutase (SOD3) activity, protein, metabolites of the nitric oxide/cyclic GMP pathway, heme oxygenase-I and inducible nitric oxide synthase expression in aqueous humor or/and peripheral blood from fifty-six patients with retinitis pigmentosa and sixty subjects without systemic or ocular oxidative stress-related disease. Multivariate analysis of covariance revealed that retinitis pigmentosa alters ocular antioxidant defence machinery and the redox status in blood. Patients with retinitis pigmentosa present low total antioxidant capacity including reduced SOD3 activity and protein concentration in aqueous humor. Patients also show reduced SOD3 activity, increased TBARS formation and upregulation of the nitric oxide/cyclic GMP pathway in peripheral blood. Together these findings confirmed the hypothesis that patients with retinitis pigmentosa present reduced ocular antioxidant status. Moreover, these patients show changes in some oxidative-nitrosative markers in the peripheral blood. Further studies are needed to clarify the relationship between these peripheral markers and retinitis pigmentosa.