Transport of β-amyloid from brain to eye causes retinal degeneration in Alzheimer's disease.

IF 12.6 1区医学 Q1 IMMUNOLOGY

Journal of Experimental Medicine Pub Date : 2024-11-04 Epub Date: 2024-09-24 DOI:10.1084/jem.20240386

Qiuchen Cao, Shige Yang, Xiaowei Wang, Huaiqing Sun, Weijie Chen, Yuliang Wang, Junying Gao, Yanchi Wu, Qiuhua Yang, Xue Chen, Songtao Yuan, Ming Xiao, Maiken Nedergaard, Yuqing Huo, Qinghuai Liu

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Abstract

The eye is closely connected to the brain, providing a unique window to detect pathological changes in the brain. In this study, we discovered β-amyloid (Aβ) deposits along the ocular glymphatic system in patients with Alzheimer's disease (AD) and 5×FAD transgenic mouse model. Interestingly, Aβ from the brain can flow into the eyes along the optic nerve through cerebrospinal fluid (CSF), causing retinal degeneration. Aβ is mainly observed in the optic nerve sheath, the neural axon, and the perivascular space, which might represent the critical steps of the Aβ transportation from the brain to the eyes. Aquaporin-4 facilitates the influx of Aβ in brain-eye transport and out-excretion of the retina, and its absence or loss of polarity exacerbates brain-derived Aβ induced damage and visual impairment. These results revealed brain-to-eye Aβ transport as a major contributor to AD retinopathy, highlighting a new therapeutic avenue in ocular and neurodegenerative disease.

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从大脑到眼睛的β-淀粉样蛋白运输导致阿尔茨海默氏症患者视网膜退化。

眼睛与大脑紧密相连，为检测大脑病理变化提供了一个独特的窗口。在这项研究中，我们在阿尔茨海默病患者和 5×FAD 转基因小鼠模型中发现了β淀粉样蛋白（Aβ）沿眼部淋巴系统沉积。有趣的是，大脑中的 Aβ 可通过脑脊液（CSF）沿视神经流入眼睛，导致视网膜变性。Aβ主要存在于视神经鞘、神经轴突和血管周围间隙，这可能是Aβ从大脑运输到眼睛的关键步骤。Aquaporin-4有助于Aβ在脑-眼运输过程中的流入和视网膜的排出，其缺失或极性丧失会加剧脑源性Aβ诱导的损伤和视力障碍。这些结果揭示了脑-眼Aβ转运是导致AD视网膜病变的主要因素，为眼部和神经退行性疾病的治疗开辟了一条新途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Experimental Medicine 医学-免疫学

CiteScore

26.60

自引率

1.30%

发文量

189

审稿时长

3-8 weeks

期刊介绍： Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field. Our unique editorial system, driven by a commitment to exceptional author service, involves two collaborative groups of editors: professional editors with robust scientific backgrounds and full-time practicing scientists. Each paper undergoes evaluation by at least one editor from both groups before external review. Weekly editorial meetings facilitate comprehensive discussions on papers, incorporating external referee comments, and ensure swift decisions without unnecessary demands for extensive revisions. Encompassing human studies and diverse in vivo experimental models of human disease, our focus within medical biology spans genetics, inflammation, immunity, infectious disease, cancer, vascular biology, metabolic disorders, neuroscience, and stem cell biology. We eagerly welcome reports ranging from atomic-level analyses to clinical interventions that unveil new mechanistic insights.