Endocrine Abstracts

It was reported that the inhibition of central nervous system (CNS) axon growth is mediated by Ca²⁺-dependent phosphorylation of epidermal growth factor receptor (pEGFR) and that local administration of small molecule EGFR antagonists to optic nerve lesions promoted retinal ganglion cell (RGC) axon regeneration (Koprivica et al. 2005). This result was attributed to suppression of EGFR kinase, which neutralised the axonal growth inhibitory potency of CNS myelin-derived ligands to activate the Rho/ROCK cascade after binding the NgR/p75^NTR receptor complex on axonal growth cones, but no mechanism for driving axonal regeneration was defined. We have compared the cellular distribution of pEGFR in the adult retina and optic nerve in non-regenerating and regenerating (intravitreal peripheral nerve implanted) optic nerve injury models, to evaluate whether changes in axonal pEGFR were consistent with the proposed mechanism of disinhibited RGC axonal growth. We predicted that, if pEGFR is critical for inhibitory ligand activated axonal growth cone collapse, RGC somata should localise EGFR and regenerating RGC axons contain low levels of pEGFR compared to non-regenerating axons. In both non-regenerating and regenerating optic nerve injury models pEGFR was constitutively localised to: 1), most glia in retinae and optic nerves, in which levels were enhanced after optic nerve transection; and 2), a subpopulation comprising ~30% of RGC somata, with no difference in the retinae of the two optic nerve injury models. Importantly, pEGFR was neither constitutively localised nor induced in RGC axons in the retina and optic nerve in either the non-regenerating or regenerating model, a finding that is incompatible with the contention that axonal signalling of myelin-related axon growth inhibitory ligands is pEGFR-dependent. Our results are consistent with the existence of a novel glial-dependent mechanism for EGFR-antagonist stimulated RGC axon growth.

Koprivca et al. Science 2005 310 106–110.