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Fernandino L. Vilson, Yan Guo, Jim D. Nicholson, Neil R. Miller, Steven L. Bernstein; Early Optic Nerve Inflammatory Responses in Primate NAION. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4672.
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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 primate NAION model (pNAION) to evaluate short- and long-term inflammatory responses and degree of axonal degeneration post infarct.
pNAION was generated by rose Bengal dye photoactivation by a 532 nm frequency doubled YAG laser. The lamina and posterior optic nerve regions were visualized using both H&E staining and immunohistochemistry. Inflammatory cell identification was accomplished using antibodies specific for polymorphoneutrophils (PMNs; myeloperoxidase), extrinsic macrophages (ED1+), and global inflammation , including microglia (IBA1+/ED1-). The degree of axonal degeneration was evaluated using an antibody for neurofilaments (SMI-312+).
In naive ON’s, IBA1+/ED1- (intrinsic microglia) were present with a diffuse distribution pattern throughout the ON when no axonal destruction was observed. Few, if any PMNs or ED1+/IBA1+ cells were found in the naïve ON. Three days post stroke, there was a large influx of (IBA1+/ED1+) extrinsic macrophages. These cells were concentrated in the infarct area, extending from the lamina cribrosa into the optic nerve, with marked axonal destruction, indicated by the lack of SMI312 signal in the ischemic area. We also found a concentration of PMNs within the infarcted area three days post stroke. The number of ED1+ macrophages and PMNs decreased 2-10 weeks post infarct, but moderate concentrations of IBA1+/ED1- cells remained.
Our results suggest that there is early inflammation following pNAION, which persists long after infarct initiation. Soon after ON infarct, there is a large influx of extrinsic macrophages, as well as PMNs, which was previously unsuspected. Because old world primate and human responses are similar, ON ischemia is predicted to generate an early cellular inflammatory response in humans. Currently, there are no effective treatments of NAION. However, manipulation of inflammatory responses may prove effective in reducing the amount of vision loss post stroke.
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