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Review
. 2009 Feb 6;158(3):1039-48.
doi: 10.1016/j.neuroscience.2008.07.036. Epub 2008 Jul 25.

The role of macrophages in optic nerve regeneration

Q Cui  1 , Y Yin, L I Benowitz
Affiliations
Review

The role of macrophages in optic nerve regeneration

Q Cui et al. Neuroscience. .

Abstract

Following injury to the nervous system, the activation of macrophages, microglia, and T-cells profoundly affects the ability of neurons to survive and to regenerate damaged axons. The primary visual pathway provides a well-defined model system for investigating the interactions between the immune system and the nervous system after neural injury. Following damage to the optic nerve in mice and rats, retinal ganglion cells, the projection neurons of the eye, normally fail to regenerate their axons and soon begin to die. Induction of an inflammatory response in the vitreous strongly enhances the survival of retinal ganglion cells and enables these cells to regenerate lengthy axons beyond the injury site. T cells modulate this response, whereas microglia are thought to contribute to the loss of retinal ganglion cells in this model and in certain ocular diseases. This review discusses the complex and sometimes paradoxical actions of blood-borne macrophages, resident microglia, and T-cells in determining the outcome of injury in the primary visual pathway.

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Figures

Fig. 1
Fig. 1
Intravitreal macrophage activation stimulates optic nerve regeneration. Macrophages were activated in vitreous by injecting zymosan into the eye after optic nerve crush in adult rats. Retina sections (a, c) or optic nerve sections (b, d) were immunostained with GAP-43 antibody to visualize regenerating RGCs and axons (green in a–d) and with ED-1 antibody to visualize macrophages (red in a, c) 2 weeks after the surgery. (a) Following optic nerve crush alone, there are no macrophages in retina and no GAP-43 immunostaining in RGCs (arrowheads), and (b) very few axons growing beyond the nerve crush site (asterisk). However, after zymosan treatment, (c) many macrophages are seen in the vitreous and near RGCs (arrows, red) and GAP-43 is dramatically upregulated in RGCs (arrowheads, green cells). As a result of this, (d) many GAP-43+ axons cross the nerve injury site and extend into the distal optic nerve. Scale bar=50 μm (a, c); 200 μm (b, d) (Yin et al., 2003).
Fig. 2
Fig. 2
A possible schematic time course of factors released by macrophages and RGC responsiveness. Based on the results of our previous studies, we hypothesize that (i) the net positive effect of macrophage activation peaks shortly after macrophages are activated; and (ii) RGCs show an increased responsiveness to positive-acting factors a few days after axotomy. (a) A long delay between macrophage activation and axotomy results in no axon growth. (b) Macrophage activation 3 days after axotomy produces strong regeneration.
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