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B. Slater, C. Zhang, Y. Guo, S. Bernstein; Strategies to Recruit Extrinsic Macrophages Into Post-Infarct Optic Nerves. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3242.
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Extrinsic macrophage recruitment has been shown to improve tissue recovery after optic nerve and spinal cord ischemia. The cytokine GM-CSF can recruit extrinsic macrophages. We wanted to determine whether GM-CSF administration could enhance macrophage recruitment following rodent anterior ischemic optic neuropathy (rAION), and the appropriate recruitment strategy.
rAION was induced in male Sprague-Dawley rats. Three days post rAION induction, we sterilely injected GM-CSF into either the superior colliculus (SC) or the third ventricle, using stereotactic technique. Following injection, animals were allowed to recover, and euthanized seven days post injection. Eyes were enucleated; optic nerves were cross- and longitudinally-sectioned. 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.
Post-rAION, there is transient macrophage recruitment. Extrinsic macrophages are demonstrable 3 days following post-infarct. However, extrinsic macrophage numbers fall off in the optic nerves at later times post-stroke. SC injection yielded little additional recruitment when compared with control (vehicle injected) ONs. These macrophages were present primarily in the intra-orbital portion of the ON. Third ventricle injection showed robust macrophage recruitment further along the optic nerve.
Macrophage recruitment via CSF administration may be a viable treatment option for recruiting extrinsic macrophages to the affected ON following ischemic optic neuropathy. Such an approach may enhance our ability to eliminate post-infarct degenerating myelin, and improve axonal regeneration following optic nerve stroke.
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