Suzuki Mihoko, Kamei Motohiro, Itabe Hiroyuki, Yoneda Kazuhito, Bando Hajime, Kume Noriaki, Tano Yasuo
Department of Ophthalmology, Osaka University Medical School, Suita, Japan.
Mol Vis. 2007 May 23;13:772-8.
There is good evidence that oxidative stress is involved in the pathogenesis of age-related macular degeneration (AMD). Because AMD has risk factors and histopathology similar to with atherosclerosis, we hypothesized that oxidized phospholipids, which contribute to the pathogenesis of atherosclerosis, would accumulate in the eyes of AMD patients. To test this hypothesis, we investigated whether oxidized phospholipids were present in normal eyes and whether the level changed with increasing age. We then, we determined whether the levels of oxidized phospholipids were higher in eyes with AMD.
Twenty normal human donor eyes and six eyes with AMD were studied. Immunohistochemistry was performed on a tissue strip from the macular region using an antibody against oxidized phosphatidylcholine. Western blot analysis was also performed on proteins extracted from the posterior retina of donor eyes. The immunoreactivity of the specimens and the bands were quantified with NIH image software.
Immunohistochemistry showed oxidized phosphatidylcholine was present in the photoreceptors and retinal pigment epithelium of the normal human macular area, and their levels increased with age. Eyes with AMD showed more intense immunoreactivity for oxidized phospholipids than age-matched normal eyes.
These findings suggest that oxidative stress is involved in the pathogenesis of AMD possibly by oxidizing phospholipids in the photoreceptors as demonstrated in the arterial intima of patients with atherosclerosis. It is likely that controlling oxidation of phospholipids may be a potential treatment for AMD.
有充分证据表明氧化应激参与年龄相关性黄斑变性(AMD)的发病机制。由于AMD具有与动脉粥样硬化相似的危险因素和组织病理学特征,我们推测促成动脉粥样硬化发病机制的氧化磷脂会在AMD患者的眼中蓄积。为验证这一假设,我们研究了正常眼中是否存在氧化磷脂以及其水平是否随年龄增长而变化。然后,我们确定AMD患者眼中氧化磷脂的水平是否更高。
研究了20只正常人类供体眼和6只AMD患者的眼睛。使用抗氧化磷脂酰胆碱抗体对黄斑区的组织条进行免疫组织化学检测。还对从供体眼后极部视网膜提取的蛋白质进行了蛋白质印迹分析。用NIH图像软件对标本的免疫反应性和条带进行定量分析。
免疫组织化学显示,正常人类黄斑区的光感受器和视网膜色素上皮中存在氧化磷脂酰胆碱,且其水平随年龄增长而升高。与年龄匹配的正常眼相比,AMD患者的眼睛对氧化磷脂显示出更强的免疫反应性。
这些发现表明,氧化应激可能通过氧化光感受器中的磷脂参与AMD的发病机制,这与动脉粥样硬化患者动脉内膜的情况类似。控制磷脂氧化可能是AMD的一种潜在治疗方法。