Reactive microglia and macrophage facilitate the formation of Müller glia-derived retinal progenitors.
Reactive microglia and macrophage facilitate the formation of Müller glia-derived retinal progenitors.
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作者：
Fischer, Andy J.;Zelinka, Christopher;Gallina, Donika;Scott, Melissa A.;Todd, Levi
在视网膜中，Müller胶质细胞被刺激成为祖细胞，反应性小胶质细胞总是存在。因此，我们研究了小胶质细胞/巨噬细胞的激活或消融如何影响体内视网膜中Müller胶质源性祖细胞（MGPCs）的形成。白细胞介素-6（IL-6）的眼内注射刺激了小胶质细胞/巨噬细胞的反应性，而其他类型的视网膜胶质细胞似乎基本上不受影响。在急性损伤的视网膜中，所有的视网膜小胶质细胞/巨噬细胞被消融，增殖的MGPC的形成大大减少。随着受损视网膜中小胶质细胞的消融，Notch和相关基因的水平不变或增加，而ascl 1a、TNFα、IL 1 β、补体成分3（C3）和C3 a受体的水平显著降低。在没有视网膜损伤的情况下，当小胶质细胞/巨噬细胞被消融时，胰岛素和成纤维细胞生长因子2（FGF 2）的组合未能刺激MGPC的形成。此外，眼内注射IL 6和FGF 2刺激MGPC的形成，在没有视网膜损伤的情况下，并且当小胶质细胞/巨噬细胞不存在时，MGPC的生成被阻断。我们的结论是，小胶质细胞和/或浸润的巨噬细胞的激活有助于增殖MGPCs的形成，这些作用可能是由补体系统和炎症细胞因子的成分介导的。
In retinas where Müller glia have been stimulated to become progenitor cells, reactive microglia are always present. Thus, we investigated how the activation or ablation of microglia/macrophage influences the formation of Müller glia-derived progenitor cells (MGPCs) in the retina in vivo. Intraocular injections of the Interleukin-6 (IL6) stimulated the reactivity of microglia/macrophage, whereas other types of retinal glia appear largely unaffected. In acutely damaged retinas where all of the retinal microglia/macrophage were ablated, the formation of proliferating MGPCs was greatly diminished. With the microglia ablated in damaged retinas, levels of Notch and related genes were unchanged or increased, whereas levels of ascl1a, TNFα, IL1β, complement component 3 (C3) and C3a receptor were significantly reduced. In the absence of retinal damage, the combination of insulin and Fibroblast Growth Factor 2 (FGF2) failed to stimulate the formation of MGPCs when the microglia/macrophage were ablated. In addition, intraocular injections of IL6 and FGF2 stimulated the formation of MGPCs in the absence of retinal damage, and this generation of MGPCs was blocked when the microglia/macrophage were absent. We conclude that the activation of microglia and/or infiltrating macrophage contributes to the formation of proliferating MGPCs, and these effects may be mediated by components of the complement system and inflammatory cytokines.
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影响因子：
6.2
作者：
Fischer, Andy J.;Scott, Melissa A.;Zelinka, Christopher;Sherwood, Patrick
通讯作者：
Sherwood, Patrick
影响因子：
4.7
作者：
Ghai K;Zelinka C;Fischer AJ
通讯作者：
Fischer AJ
DOI：
10.1016/j.bbrc.2012.03.139
发表时间：
2012-05-04
影响因子：
3.1
作者：
Huang T;Cui J;Li L;Hitchcock PF;Li Y
通讯作者：
Li Y
影响因子：
5.3
作者：
Fausett, Blake V.;Gumerson, Jessica D.;Goldman, Daniel
通讯作者：
Goldman, Daniel
DOI：
10.1073/pnas.1300290110
发表时间：
2013-06-04
影响因子：
11.1
作者：
Godwin, James W.;Pinto, Alexander R.;Rosenthal, Nadia A.
通讯作者：
Rosenthal, Nadia A.