Abstract
BackgroundThe 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.ResultsWe 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.ConclusionWe 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.
Highlights
The hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) plays a crucial role in controlling the number of neutrophil progenitor cells
G-CSF receptor expression in retinal ganglion cells in vivo Using immunohistochemical staining with an antibody raised against the C-terminus of the G-CSFR we found expression in the retinal ganglion cell layer (Fig. 1A, C)
Prelabelling of retinal ganglion cell (RGC) by injection of a retrograde tracer (Fluorogold; Fluorochrome) into the superior colliculus, resulting in retrograde, specific staining of RGCs, demonstrated that almost all RGCs were immunoreactive for G-CSFR protein (Fig. 1D)
Summary
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 in the central nervous system. G-CSF provided neuroprotection in models of neuronal cell death. Granulocyte-Colony Stimulating Factor (G-CSF) promotes the survival, differentiation and proliferation of cells of the neutrophilic lineage [1,2]. It belongs to the group of lineage-specific hematopoietic colony growth factors. In the central nervous system (CNS) G-CSF is produced endogenously by neurons and its production can be enhanced by exogenous stimuli such as hypoxia [3]. Long-term application of GCSF for patients with chronic neutropenia was safe, in regard to hematological malignancies [5,6,7,8]
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