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Lgr5⁺无长突细胞在成年小鼠视网膜中具有再生潜力。

Lgr5⁺ amacrine cells possess regenerative potential in the retina of adult mice.

作者信息

Chen Mengfei, Tian Shenghe, Glasgow Nathan G, Gibson Gregory, Yang Xiaoling, Shiber Christen E, Funderburgh James, Watkins Simon, Johnson Jon W, Schuman Joel S, Liu Hongjun

机构信息

Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Department of Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

出版信息

Aging Cell. 2015 Aug;14(4):635-43. doi: 10.1111/acel.12346. Epub 2015 May 20.

Abstract

Current knowledge indicates that the adult mammalian retina lacks regenerative capacity. Here, we show that the adult stem cell marker, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), is expressed in the retina of adult mice. Lgr5(+) cells are generated at late stages of retinal development and exhibit properties of differentiated amacrine interneurons (amacrine cells). Nevertheless, Lgr5(+) amacrine cells contribute to regeneration of new retinal cells in the adult stage. The generation of new retinal cells, including retinal neurons and Müller glia from Lgr5(+) amacrine cells, begins in early adulthood and continues as the animal ages. Together, these findings suggest that the mammalian retina is not devoid of regeneration as previously thought. It is rather dynamic, and Lgr5(+) amacrine cells function as an endogenous regenerative source. The identification of such cells in the mammalian retina may provide new insights into neuronal regeneration and point to therapeutic opportunities for age-related retinal degenerative diseases.

摘要

目前的知识表明,成年哺乳动物的视网膜缺乏再生能力。在此,我们表明成年干细胞标志物富含亮氨酸重复序列的G蛋白偶联受体5(Lgr5)在成年小鼠的视网膜中表达。Lgr5(+)细胞在视网膜发育后期产生,并表现出分化的无长突中间神经元(无长突细胞)的特性。然而,Lgr5(+)无长突细胞有助于成年期新视网膜细胞的再生。从Lgr5(+)无长突细胞产生包括视网膜神经元和穆勒胶质细胞在内的新视网膜细胞,始于成年早期,并随着动物年龄的增长而持续。总之,这些发现表明哺乳动物的视网膜并非如之前所认为的那样缺乏再生能力。它相当具有动态性,并且Lgr5(+)无长突细胞作为内源性再生源发挥作用。在哺乳动物视网膜中鉴定出此类细胞可能为神经元再生提供新的见解,并为与年龄相关的视网膜退行性疾病指明治疗机会。

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