Optic nerve as a source of activated retinal microglia post-injury.
Optic nerve as a source of activated retinal microglia post-injury.
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DOI：
10.1186/s40478-018-0571-8
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发表时间：
2018-07-23
影响因子：
7.1
通讯作者：
Gregerson DS
中科院分区：
文献类型：
--
作者：
Heuss ND;Pierson MJ;Roehrich H;McPherson SW;Gram AL;Li L;Gregerson DS
使用从转基因 CD11c 启动子表达绿色荧光蛋白 (GFP) 的小鼠，我们发现受控的视神经挤压 (ONC) 损伤将 GFPhi 视网膜骨髓细胞吸引到垂死的视网膜神经节细胞及其轴突。然而，这些视网膜骨髓细胞的起源尚不清楚。在这项研究中，我们使用转基因小鼠结合 ONC、部分和全部视神经横断 (ONT) 以及联体共生来确定损伤诱导的视网膜骨髓细胞的起源。对共生小鼠的分析和命运图谱表明，做出反应的视网膜骨髓细胞并非源自循环巨噬细胞，并且 GFPhi 骨髓细胞可能源自 GFPlo 小胶质细胞。 ONC 后视神经与视网膜的比较显示，视神经中 GFPhi 细胞和 GFPlo 小胶质细胞的浓度要高得多。视神经损伤还会在视神经中诱导 Ki67+ 细胞，但在视网膜中则不会。完全ONT与部分ONT后视网膜髓样细胞反应的比较显示，完全ONT后视网膜中的GFPhi细胞和GFPlo小胶质细胞较少，尽管这是更严重的损伤，这表明视神经的完全横断可以阻止响应的髓样细胞迁移到视网膜。我们的研究结果表明，视神经损伤后，视神经可以成为视网膜中激活的小胶质细胞和其他视网膜髓样细胞的储存库。本文的在线版本 (10.1186/s40478-018-0571-8) 包含补充材料，可供授权用户使用。
Using mice expressing green fluorescent protein (GFP) from a transgenic CD11c promoter we found that a controlled optic nerve crush (ONC) injury attracted GFPhi retinal myeloid cells to the dying retinal ganglion cells and their axons. However, the origin of these retinal myeloid cells was uncertain. In this study we use transgenic mice in conjunction with ONC, partial and full optic nerve transection (ONT), and parabiosis to determine the origin of injury induced retinal myeloid cells. Analysis of parabiotic mice and fate mapping showed that responding retinal myeloid cells were not derived from circulating macrophages and that GFPhi myeloid cells could be derived from GFPlo microglia. Comparison of optic nerve to retina following an ONC showed a much greater concentration of GFPhi cells and GFPlo microglia in the optic nerve. Optic nerve injury also induced Ki67+ cells in the optic nerve but not in the retina. Comparison of the retinal myeloid cell response after full versus partial ONT revealed fewer GFPhi cells and GFPlo microglia in the retina following a full ONT despite it being a more severe injury, suggesting that full transection of the optic nerve can block the migration of responding myeloid cells to the retina. Our results suggest that the optic nerve can be a reservoir for activated microglia and other retinal myeloid cells in the retina following optic nerve injury. The online version of this article (10.1186/s40478-018-0571-8) contains supplementary material, which is available to authorized users.
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影响因子：
30.5
作者：
Goldmann T;Wieghofer P;Jordão MJ;Prutek F;Hagemeyer N;Frenzel K;Amann L;Staszewski O;Kierdorf K;Krueger M;Locatelli G;Hochgerner H;Zeiser R;Epelman S;Geissmann F;Priller J;Rossi FM;Bechmann I;Kerschensteiner M;Linnarsson S;Jung S;Prinz M
通讯作者：
Prinz M
影响因子：
6.1
作者：
Fernandes, Kimberly A.;Harder, Jeffrey M.;Fornarola, Laura B.;Freeman, Robert S.;Clark, Abbot F.;Pang, Iok-Hou;John, Simon W. M.;Libby, Richard T.
通讯作者：
Libby, Richard T.
影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
影响因子：
6
作者：
Joly, Sandrine;Francke, Mike;Reme, Charlotte E.
通讯作者：
Reme, Charlotte E.
影响因子：
5.5
作者：
Domingues HS;Portugal CC;Socodato R;Relvas JB
通讯作者：
Relvas JB