Both systemic and local application of Granulocyte-colony stimulating factor (G-CSF) is neuroprotective after retinal ganglion cell axotomy
Both systemic and local application of Granulocyte-colony stimulating factor (G-CSF) is neuroprotective after retinal ganglion cell axotomy
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DOI：
10.1186/1471-2202-10-49
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发表时间：
2009-05-14
期刊：
影响因子：
2.4
通讯作者：
Weishaupt, Jochen H.
中科院分区：
文献类型：
--
作者：
Frank, Tobias;Schlachetzki, Johannes C. M.;Weishaupt, Jochen H.
背景：造血粒细胞集落刺激因子（G-CSF）在控制中性粒细胞祖细胞数量方面发挥着至关重要的作用。其功能是通过 G-CSF 受体介导的，最近发现 G-CSF 受体也在中枢神经系统中表达。此外，G-CSF 在神经元细胞死亡模型中提供神经保护。在这里，我们使用视网膜神经节细胞（RGC）轴切术模型来比较神经保护分子的局部和全身应用的效果。结果：我们发现G-CSF受体在体内和体外由RGC强烈表达。因此，我们评估了 G-CSF 作为 RGC 的神经保护剂，发现皮下给予 G-CSF 对轴突 RGC 具有剂量依赖性神经保护作用。由于干细胞动员先前已被讨论为 G-CSF 神经保护作用的可能贡献者，因此我们比较了通过将 G-CSF 注射到玻璃体中的 RGC 局部治疗与皮下应用的全身递送。两种应用途径都将视网膜神经节细胞死亡减少到相当的程度。此外，G-CSF 增强了免疫纯化的 RGC 的体外存活率。 结论：我们因此表明，G-CSF 的神经保护作用至少部分独立于潜在的全身效应，并提供了进一步的证据，表明临床适用的 G-CSF 可以成为神经退行性疾病和青光眼的治疗选择。
Background: The hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) plays a crucial role in controlling the number of neutrophil progenitor cells. Its function is mediated via the G-CSF receptor, which was recently found to be expressed also in the central nervous system. In addition, G-CSF provided neuroprotection in models of neuronal cell death. Here we used the retinal ganglion cell (RGC) axotomy model to compare effects of local and systemic application of neuroprotective molecules.Results: We found that the G-CSF receptor is robustly expressed by RGCs in vivo and in vitro. We thus evaluated G-CSF as a neuroprotectant for RGCs and found a dose-dependent neuroprotective effect of G-CSF on axotomized RGCs when given subcutaneously. As stem stell mobilization had previously been discussed as a possible contributor to the neuroprotective effects of G-CSF, we compared the local treatment of RGCs by injection of G-CSF into the vitreous body with systemic delivery by subcutaneous application. Both routes of application reduced retinal ganglion cell death to a comparable extent. Moreover, G-CSF enhanced the survival of immunopurified RGCs in vitro.Conclusion: We thus show that G-CSF neuroprotection is at least partially independent of potential systemic effects and provide further evidence that the clinically applicable G-CSF could become a treatment option for both neurodegenerative diseases and glaucoma.