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Fernandino L. Vilson, Bernard Slater, Danny Weinreich, Neil R. Miller, Steven L. Bernstein; GM-CSF is Neuroprotective in a Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy (rAION). Invest. Ophthalmol. Vis. Sci. 2012;53(14):2979.
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Nonarteritic anterior ischemic optic neuropathy (NAION) is a white matter ischemic infarct of the optic nerve (ON), characterized by a sudden loss of vision in one or both eyes. We utilized the rodent NAION model (rAION) to evaluate the effects of a granulocyte macrophage colony stimulating factor (GM-CSF) as a form of long-term neuroprotection post infarct.
rAION was generated by rose Bengal dye-coupled photoactivation by a 532 nm frequency doubled YAG laser. GM-CSF was administered intraventricularly three days post-induction.The lamina and posterior optic nerve regions were visualized using both H&E staining and immunohistochemistry. Inflammatory cell identification and distribution pattern was accomplished using antibodies specific for extrinsic macrophages (ED1+), and global inflammation, including microglia (IBA1+/ED1-). The degree of axonal degeneration was evaluated using an antibody for neurofilaments (SMI-312+). Retinal ganglion cell (RGC) stereology was evaluated at 30 days post-induction using Stereoinvestigator linked to Nikon E800 microscope with a computer-driven stage.
In naive ON’s, intrinsic microglia were present with a diffuse distribution pattern throughout the ON. Few, if any extrinsic macrophages (ED1+/IBA1+) cells were found in the naïve ON. In vehicle treated animals 7 days post stroke, there was an influx of extrinsic macrophages. These cells were concentrated in the infarct area, with marked axonal destruction, indicated by the lack of SMI312 signal in the ischemic area. In GM-CSF treated animals 7 days post stroke, we found a large influx of extrinsic macrophages in the ischemic area. These cells were spread through out the nerve and were not restricted to the infarcted area. RGC stereology reveals an increased number of surviving RGCs in treated animals compared with vehicle-treated animals.
Our results suggest that treatment of NAION rodent models with GM-CSF shows a neuroprotective long-term effect that includes both RGCs and their axons. Immunomodulation of post-ON infarct inflammation may be an appropriate therapeutic approach for NAION.
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