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微生物组与遗传性视网膜变性

Microbiome and Inherited Retinal Degenerations.

作者信息

Douglas Vivian P, Douglas Konstantinos A A, Iannaccone Alessandro

机构信息

Department of Ophthalmology, Athens Naval Hospital, Athens, Greece.

1st Department of Ophthalmology, "G. Gennimatas" General Hospital, National and Kapodistrian University of Athens, Athens, Greece.

出版信息

Am J Pathol. 2023 Nov;193(11):1669-1674. doi: 10.1016/j.ajpath.2023.03.005. Epub 2023 Apr 5.

Abstract

Inherited retinal degenerations (IRDs) represent a genetically and clinically heterogeneous group of progressive and visually debilitating disorders that can lead to irreversible visual loss. Our understanding of IRD pathogenesis at both the genetic and cellular levels has increased tremendously over the past two decades, but the exact pathogenic mechanisms remain incompletely understood. Enhanced understanding of the pathophysiology of these diseases can result in new treatment targets. Alterations in the human gut microbiome play a key role in the pathogenesis of many ocular and nonocular diseases, such as age-related macular degeneration, neurologic and metabolic disorders, and autoimmune conditions. The gut microbiome regulates the susceptibility of mice to develop experimental autoimmune uveitis, a model for autoimmune disease of the posterior portion of the eye elicited by the systemic response to retinal antigens. Because of the mounting evidence in favor of a role for local and systemic inflammatory and autoimmune-mediated components to IRD pathogenesis, this review presents the current knowledge of gut microbiome in IRDs and discusses the association between possible changes in gut microbiome and pathogenesis of these diseases, with special attention to their possible contribution to the inflammatory underpinnings of IRDs.

摘要

遗传性视网膜变性(IRD)是一组在遗传和临床上具有异质性的进行性视觉障碍疾病,可导致不可逆的视力丧失。在过去二十年中,我们对IRD在遗传和细胞水平上的发病机制的理解有了极大的提高,但确切的致病机制仍未完全清楚。对这些疾病病理生理学的深入理解可以带来新的治疗靶点。人类肠道微生物群的改变在许多眼部和非眼部疾病的发病机制中起关键作用,如年龄相关性黄斑变性、神经和代谢紊乱以及自身免疫性疾病。肠道微生物群调节小鼠发生实验性自身免疫性葡萄膜炎的易感性,实验性自身免疫性葡萄膜炎是一种由对视网膜抗原的全身反应引发的眼后部自身免疫性疾病模型。由于越来越多的证据支持局部和全身炎症及自身免疫介导成分在IRD发病机制中的作用,本综述介绍了目前关于IRD中肠道微生物群的知识,并讨论了肠道微生物群可能的变化与这些疾病发病机制之间的关联,特别关注它们对IRD炎症基础的可能贡献。

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