Izzotti Alberto, Saccà Sergio C, Longobardi Mariagrazia, Cartiglia Cristina
Department of Health Sciences, Faculty of Medicine, University of Genoa, Genoa, Italy.
Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5251-8. doi: 10.1167/iovs.09-3871. Epub 2009 Jun 10.
The anterior chamber of the eye is a highly specialized structure delimited by the cornea, lens, and iris. It contains the aqueous humor, secreted by the ciliary body and drained by the trabecular meshwork. Alteration of aqueous humor homeostasis plays a major role in the pathogenesis of glaucoma. The trabecular meshwork is the target tissue of glaucoma in the anterior chamber, and the development and progression of glaucoma are accompanied by accumulation of oxidative damage in this tissue. This study was conducted to comparatively evaluate the sensitivity to oxidative stress of anterior chamber tissues including the cornea, iris, and trabecular meshwork.
Cornea, iris, and trabecular meshwork fragments collected from six cornea donors were either left untreated or treated with hydrogen peroxide. Oxidative damage was determined by evaluating nucleotide oxidative modifications (8-hydroxy-2'-deoxyguanosine) and apurinic alkali-fragile sites by capillary electrophoresis.
The results indicated that the basal level of oxidative nucleotide modifications was higher in the cornea than in the iris and trabecular meshwork. The trabecular meshwork was the most sensitive tissue to oxidative damage, as after exposure to hydrogen peroxide both markers of oxidative damage dramatically increased in the trabecular meshwork but not in the cornea and iris.
Because the cornea and iris are directly exposed to light, they possess antioxidant defense mechanisms that are not activated in the trabecular meshwork. The peculiar sensitivity of the trabecular meshwork to oxidative stress is consistent with the damage selectively induced in it, triggering glaucoma's pathogenic cascade.
眼球前房是一个由角膜、晶状体和虹膜界定的高度特殊的结构。它含有由睫状体分泌并经小梁网引流的房水。房水动态平衡的改变在青光眼发病机制中起主要作用。小梁网是前房中青光眼的靶组织,青光眼的发生和发展伴随着该组织中氧化损伤的积累。本研究旨在比较评估包括角膜、虹膜和小梁网在内的前房组织对氧化应激的敏感性。
从六名角膜捐献者收集的角膜、虹膜和小梁网碎片,要么不进行处理,要么用过氧化氢处理。通过毛细管电泳评估核苷酸氧化修饰(8-羟基-2'-脱氧鸟苷)和脱嘌呤碱敏感位点来确定氧化损伤。
结果表明,角膜中氧化核苷酸修饰的基础水平高于虹膜和小梁网。小梁网是对氧化损伤最敏感的组织,因为在接触过氧化氢后,小梁网中氧化损伤的两个标志物都显著增加,而角膜和虹膜中则没有。
由于角膜和虹膜直接暴露于光线下,它们具有在小梁网中未被激活的抗氧化防御机制。小梁网对氧化应激的特殊敏感性与在其中选择性诱导的损伤一致,引发青光眼的致病级联反应。