Cigarette smoke-related oxidants and the development of sub-RPE deposits in an experimental animal model of dry AMD
Cigarette smoke-related oxidants and the development of sub-RPE deposits in an experimental animal model of dry AMD
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DOI：
10.1167/iovs.05-0719
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发表时间：
2006-02-01
影响因子：
4.4
通讯作者：
Cousins, SW
中科院分区：
文献类型：
--
作者：
Espinosa-Heidmann, DG;Suner, IJ;Cousins, SW
目的。视网膜色素上皮（RPE）的氧化损伤被认为是与年龄相关性黄斑变性（AMD）中视网膜下沉积物积累相关的重要损伤刺激。吸烟是 AMD 的主要危险因素，与香烟烟雾相关的焦油含有高浓度的强氧化剂对苯二酚 (HQ)。本研究旨在调查香烟烟雾 (CS) 和 HQ 对实验小鼠模型中亚 RPE 沉积物发育的影响。方法。 16 个月大的 C57BL/6 雌性小鼠被喂食高脂肪饮食 (HFD) 4.5 个月。将小鼠分为两个主要实验组，一组用于检查香烟烟雾的影响，一组用于研究特定香烟烟雾成分（例如 HQ）的影响。在第一组中，小鼠的眼睛暴露于蓝绿光（阳性对照）或整个香烟烟雾中。没有干预的第三组作为阴性对照。在第二个实验组中，动物接受含有低脂肪或高脂肪含量的 HQ (0.8%) 的纯化饮食，持续 4.5 个月。两组小鼠在 4.5 个月时均被处以安乐死，并对眼睛进行透射电子显微镜检查。 结果。正如我们实验室和其他实验室先前所证明的那样，大多数在没有接触其他氧化剂的情况下喂食 HFD 的小鼠表现出正常的形态，或者在少数情况下表现出小结节状基底层状沉积物。暴露于全部香烟烟雾或食物中的 HQ 的小鼠的眼睛表现出不同程度的基底层状沉积物和弥漫性增厚的布鲁赫膜。脉络膜毛细血管内皮不同程度地肥厚。结论。暴露于香烟烟雾或与烟雾相关的氧化还原分子 HQ 会导致亚 RPE 沉积物的形成、布鲁赫膜增厚以及沉积物在布鲁赫膜内积聚。与烟雾相关的氧化剂可能是对脉络膜毛细血管和 RPE 的另一种氧化损伤刺激物，并且可以解释吸烟与早期 AMD 之间的关联。
PURPOSE. Oxidative injury to the retinal pigment epithelium (RPE) has been proposed to be an important injury stimulus relevant to the accumulation of subretinal deposits in age-related macular degeneration (AMD). Cigarette smoking is a major risk factor for AMD, and cigarette smoke-related tar contains high concentrations of a potent oxidant, hydroquinone (HQ). This study was an investigation of the effects of cigarette smoke (CS) and HQ in the development of sub-RPE deposits in an experimental mouse model.METHODS. Sixteen-month-old C57BL/6 female mice were fed a high-fat diet (HFD) for 4.5 months. Mice were divided into two major experimental groups, one to examine the effects of cigarette smoke and one to study the effects of a defined cigarette smoke component such as HQ. In the first group, mice eyes were exposed to blue-green light (positive controls) or to whole cigarette smoke. A third group with no intervention served as the negative control. In the second experimental group, animals received a purified diet with HQ (0.8%) with low or high fat content for 4.5 months. Mice in both groups were euthanatized at 4.5 months and eyes processed for transmission electron microscopy.RESULTS. As previously demonstrated by our laboratory and others, most mice fed an HFD without other oxidant exposure demonstrated normal morphology or, in a few cases, small nodular basal laminar deposits. Eyes of mice exposed to whole cigarette smoke or to HQ in the food demonstrated a variable degree of basal laminar deposits and diffusely thickened Bruch's membrane. The choriocapillaris endothelium was variably hypertrophic.CONCLUSIONS. Exposure to cigarette smoke or the smoke-related redox molecule, HQ, results in the formation of sub-RPE deposits, thickening of Bruch's membrane, and accumulation of deposits within Bruch's membrane. Smoke-related oxidants may be another oxidative injury stimulus to the choriocapillaris and RPE, and may explain the association between cigarette smoking and early AMD.