Fischer Andy J, Zelinka Christopher, Gallina Donika, Scott Melissa A, Todd Levi
Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio.
Glia. 2014 Oct;62(10):1608-28. doi: 10.1002/glia.22703. Epub 2014 Jun 10.
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.
在 Müller 胶质细胞已被刺激成为祖细胞的视网膜中，总有反应性小胶质细胞存在。因此，我们研究了小胶质细胞/巨噬细胞的激活或清除如何在体内影响视网膜中 Müller 胶质细胞衍生的祖细胞（MGPCs）的形成。眼内注射白细胞介素-6（IL6）可刺激小胶质细胞/巨噬细胞的反应性，而其他类型的视网膜胶质细胞在很大程度上似乎未受影响。在所有视网膜小胶质细胞/巨噬细胞均被清除的急性损伤视网膜中，增殖性 MGPCs 的形成显著减少。在损伤视网膜中清除小胶质细胞后，Notch 及相关基因的水平未改变或升高，而 ascl1a、TNFα、IL1β、补体成分 3（C3）和 C3a 受体的水平显著降低。在无视网膜损伤的情况下，当小胶质细胞/巨噬细胞被清除时，胰岛素和成纤维细胞生长因子 2（FGF2）的组合未能刺激 MGPCs 的形成。此外，眼内注射 IL6 和 FGF2 在无视网膜损伤时可刺激 MGPCs 的形成，而当不存在小胶质细胞/巨噬细胞时，这种 MGPCs 的生成被阻断。我们得出结论，小胶质细胞和/或浸润性巨噬细胞的激活有助于增殖性 MGPCs 的形成，并且这些作用可能由补体系统和炎性细胞因子的成分介导。
