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[氧化应激与假性剥脱性青光眼]

[Oxidative stress and pseudoexfoliation glaucoma].

作者信息

Schlötzer-Schrehardt U

机构信息

Augenklinik, Universität Erlangen-Nürnberg.

出版信息

Klin Monbl Augenheilkd. 2010 Feb;227(2):108-13. doi: 10.1055/s-0028-1109977. Epub 2010 Feb 12.

DOI:10.1055/s-0028-1109977
PMID:20155654
Abstract

Pseudoexfoliation (PEX) glaucoma is the most common identifiable cause of open-angle glaucoma worldwide, comprising the majority of glaucoma in some countries. The underlying disorder, PEX syndrome, is a generalised, genetically determined, elastotic process of the extracellular matrix characterised by the excessive production and progressive accumulation of a fibrillar material in various tissues including the outflow pathways. Increasing evidence suggests that the oxidative-antioxidative balance is disturbed in patients with PEX syndrome/glaucoma, both in the anterior segment and throughout the body, and that the resulting oxidative stress constitutes a major mechanism involved in the pathophysiology of this fibrotic process. Significantly reduced levels of antioxidants, such as ascorbic acid, glutathione, trace elements, antioxidative enzymes, and total antioxidative capacity in aqueous humor and serum suggest a faulty antioxidative defense system in PEX patients. The down-regulation of antioxidative enzymes in anterior segment tissues also indicates an inadequate cytoprotection against oxidative stress. Concomitantly, levels of oxidants such as hydrogen peroxide or nitric oxide, and oxidative stress markers, including lipid peroxidation products, degradation products of oxidated and methylated proteins, advanced glycation end products, and homocysteine are significantly increased in aqueous humor, tissues, and serum. The available data suggest that chronic oxidative stress in combination with weakened cytoprotective and repair strategies affects the abnormal matrix metabolism by induction of a persistent pro-inflammatory state and activation of the profibrotic growth factor TGF-beta1. Oxidative stress, therefore, appears to represent a modifiable risk factor in the management of patients with PEX syndrome/glaucoma.

摘要

假性剥脱性(PEX)青光眼是全球开角型青光眼最常见的可识别病因,在一些国家占青光眼患者的大多数。潜在疾病,即PEX综合征,是一种全身性、由基因决定的细胞外基质弹性组织变性过程,其特征是在包括房水流出通道在内的各种组织中过度产生并逐渐积累一种纤维状物质。越来越多的证据表明,PEX综合征/青光眼患者在前房和全身的氧化-抗氧化平衡均受到干扰,由此产生的氧化应激是参与这种纤维化过程病理生理学的主要机制。房水和血清中抗氧化剂(如抗坏血酸、谷胱甘肽、微量元素、抗氧化酶和总抗氧化能力)水平显著降低,提示PEX患者的抗氧化防御系统存在缺陷。前房组织中抗氧化酶的下调也表明对氧化应激的细胞保护不足。与此同时,房水、组织和血清中的氧化剂(如过氧化氢或一氧化氮)以及氧化应激标志物(包括脂质过氧化产物、氧化和甲基化蛋白质的降解产物、晚期糖基化终产物和同型半胱氨酸)水平显著升高。现有数据表明,慢性氧化应激与细胞保护和修复策略减弱相结合,通过诱导持续的促炎状态和激活促纤维化生长因子TGF-β1来影响异常的基质代谢。因此,氧化应激似乎是PEX综合征/青光眼患者管理中一个可改变的危险因素。

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