Characterization of Immune Cells and Molecules that Promote and Suppress CNS Axon Regeneration

Abstract

In adult mammals, injured retinal ganglion cells (RGCs) fail to spontaneously regrow severed axons, resulting in permanent visual deficits. Robust axon growth, however, is observed after intra-ocular injection of particulate β-glucan isolated from yeast. Blood-borne myeloid cells rapidly respond to β-glucan, releasing numerous pro-regenerative factors. Unfortunately, the pro-regenerative effects are undermined by retinal damage inflicted by an overactive immune system. In my presentation I will show that protection of the inflamed vasculature promotes immune-mediated RGC regeneration. In the absence of microglia, leakiness of the blood-retina barrier increases, pro-inflammatory neutrophils are elevated, and RGC regeneration is reduced. Functional ablation of the complement receptor 3 (CD11b/integrin-αM), but not the complement components C1q^-/- or C3^-/-, reduces ocular inflammation, protects the blood-retina barrier, and enhances RGC regeneration. Selective targeting of neutrophils with anti-Ly6G does not increase axogenic neutrophils but protects the blood-retina barrier and enhances RGC regeneration. Selective blocking of blood-borne monocytes from entering the eye upon ocular β-glucan administration resulted in significantly reduced RGC axon regeneration. Together, these findings reveal pro-regenerative and detrimental activities of specific myeloid cell populations toward injured CNS neurons and show that protection of the inflamed vasculature promotes neuronal regeneration.

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