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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration
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Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration

机译：小鼠血浆铜蓝蛋白和肝素的破坏会导致视网膜铁超载和视网膜变性，并伴有年龄相关性黄斑变性

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Mechanisms of brain and retinal iron homeostasis have become subjects of increased interest after the discovery of elevated iron levels in brains of patients with Alzheimer's disease and retinas of patients with age-related macular degeneration. To determine whether the ferroxidase ceruloplasmin (Cp) and its homolog hephaestin (Heph) are important for retinal iron homeostasis, we studied retinas from mice deficient in Cp and/or Heph. In normal mice, Cp and Heph localize to Muller glia and retinal pigment epithelium, a blood-brain barrier. Mice deficient in both Cp and Heph, but not each individually, had a striking, age-dependent increase in retinal pigment epithelium and retinal iron. The iron storage protein ferritin was also increased in Cp-/-Heph-/Y retinas. After retinal iron levels had increased, Cp-/-Heph-/Y mice had age-dependent retinal pigment epithelium hypertrophy, hyperplasia and death, photoreceptor degeneration, and subretinal neovascularization, providing a model of some features of the human retinal diseases aceruloplasminemia and age-related macular degeneration. This pathology indicates that Cp and Heph are critical for CNS iron homeostasis and that loss of Cp and Heph in the mouse leads to age-dependent retinal neurodegeneration, providing a model that can be used to test the therapeutic efficacy of iron chelators and antiangiogenic agents.
机译：在阿尔茨海默氏病患者的大脑和与年龄相关的黄斑变性的患者的视网膜中发现铁水平升高后，大脑和视网膜铁稳态的机制已成为人们关注的主题。为了确定铁过氧化物酶铜蓝蛋白（Cp）及其同源肝素（Heph）对视网膜铁稳态是否重要，我们研究了Cp和/或Heph缺陷小鼠的视网膜。在正常小鼠中，Cp和Heph定位于Muller胶质细胞和视网膜色素上皮（血脑屏障）。 Cp和Heph均缺乏的小鼠，但并非单独存在，其视网膜色素上皮和视网膜铁显着地，年龄依赖性地增加。铁存储蛋白铁蛋白在Cp-/-Heph- / Y视网膜中也增加。视网膜铁水平升高后，Cp-/-Heph- / Y小鼠具有年龄依赖性的视网膜色素上皮肥大，增生和死亡，感光细胞变性和视网膜下新生血管形成，从而提供了人类视网膜疾病铜绿蛋白血症和年龄的某些特征的模型相关的黄斑变性。此病理表明，Cp和Heph对于CNS铁稳态至关重要，并且小鼠中Cp和Heph的丧失会导致年龄依赖性视网膜神经变性，从而提供了可用于测试铁螯合剂和抗血管生成剂治疗功效的模型。

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