This review will describe the unique advantages that are offered by
the visual system of mammals and other vertebrates for studying the
regenerative responses of the central nervous system (CNS) to injury, and
recent insights provided by such studies. In the mouse and rat visual system a
variety of experimental paradigms promote survival of retinal ganglion cells
(RGC) and optic nerve regeneration, probably through stimulation by
neurotrophic factors (NTF) either directly, or indirectly through retinal
astrocyte/Müller cell intermediary activation. NTF induce disinhibition of
axon growth through regulated intramembranous proteolysis of p75
$^{NTR}$
,
and the inactivation of RhoA and EGFR signalling. The
concomitant release of metalloproteinases (MMP) and plasminogen activators from
RGC axons, and tissue inhibitors of metalloproteinases from optic nerve glia
repress scarring and thereby reduce titres of scar-derived inhibitory ligands
expressed in the wound. MMP also degrade myelin-derived inhibitory ligands
along regenerating axon trajectories after regulated release from glia at the
growing front of regenerating RGC axons. Optic nerve transection induces
apoptosis of RGC which is blocked by anti-apoptotic regimes and thus, in
combination with blockers of axon-growth inhibitory signalling and promoters of
axon growth may be a therapeutic formula for promoting sustained axon
regeneration. All these findings in the visual system are translatable to the
CNS as a whole and thus strategies that successfully promote visual axon
regeneration will be equally effective elsewhere in the CNS. Future
developments likely to advance the field of regenerative research include a
greater understanding of phylogenetic differences in the response of the CNS to
injury, the role of NTF, cAMP, EGFR, glia/neuron interactions in disinhibiting
and promoting axon growth, the control of neuron death, and effective drug
delivery.
