Both systemic and local application of granulocyte-colony stimulating factor (G-CSF) is neuroprotective after retinal ganglion cell axotomy.
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.


CONCLUSIONS
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.
Frank
Tobias
T
Department of Neurology, University Medical Center Göttingen, Göttingen, Germany. tobias.frank@med.uni-goettingen.de
Schlachetzki
Johannes C M
JC
Göricke
Bettina
B
Meuer
Katrin
K
Rohde
Gundula
G
Dietz
Gunnar P H
GP
Bähr
Mathias
M
Schneider
Armin
A
Weishaupt
Jochen H
JH
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019771:Axotomy; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000502:physiology*; D007279:Injections, Subcutaneous; D009410:Nerve Degeneration / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D020221:Optic Nerve Injuries / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism; D018709:Statistics, Nonparametric; D014822:Vitreous Body / Q000187:drug effects
D018696:Neuroprotective Agents; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor