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B. Slater, Y. Guo, C. Zhang, S. L. Bernstein; Effect of GM-CSF Recruitment of Extrinsic Macrophages into Post-infarct Optic Nerves. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3230.
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Extrinsic macrophage recruitment can protect retinal ganglion cell (RGC) neurons and improve tissue recovery after optic nerve and spinal cord damage. The cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) can recruit extrinsic macrophages. We wanted to determine whether GM-CSF administration can enhance macrophage recruitment following rodent anterior ischemic optic neuropathy (rAION), and whether this enhance RGC survival.
rAION was induced in male Sprague-Dawley rats to a predicted level of 35-50% RGC loss. Three days post rAION induction, we sterilely injected either GM-CSF (n=8) or vehicle (sterile saline) into the third ventricle, using stereotactic technique. Following injection, animals were allowed to recover. Eyes were enucleated, optic nerves sectioned and retinae flat mounted. Optic nerve sections were reacted with IBA-1 (global inflammatory cell marker) and ED1 (specific for extrinsic macrophages) antibodies to reveal the extent of macrophage recruitment. Retinae were reacted with RGC specific antibody Brn3a. We performed RGC stereology using StereoInvestigator linked to an Olympus FV300 computer driven microscope stage.
rAION results in transient macrophage recruitment. Extrinsic macrophages are demonstrable 3 days following post-infarct. However, extrinsic macrophage numbers fall off in the rAION-induced optic nerves. Third ventricle injection showed robust macrophage recruitment further along the optic nerve which resulted in increased survival of RGCs post ischemia.
Macrophage recruitment via CSF administration may be a viable treatment option for recruiting extrinsic macrophages to the affected ON following ischemic optic neuropathy. This strategy may be useful for improving RGC survival post-stroke.
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