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EphA5 and ephrin-A2 expression during optic nerve regeneration: a 'two-edged sword'.

Authors: Symonds, AC  King, CE  Bartlett, CA  Sauve, Y  Lund, RD  Beazley, LD  Dunlop, SA  Rodger, J 
Citation: Symonds AC, etal., Eur J Neurosci. 2007 Feb;25(3):744-52.
Pubmed: (View Article at PubMed) PMID:17328773
DOI: Full-text: DOI:10.1111/j.1460-9568.2007.05321.x

During development, gradients of EphA receptors (nasal(low)-temporal(high)) and their ligands ephrin-As (rostral(low)-caudal(high)) are involved in establishing topography between retinal ganglion cells (RGCs) and the superior colliculus (SC). EphA5-expressing RGC axons are repulsed by ephrin-A2-expressing SC neurones. In adult rats RGCs maintain graded EphA5 expression but ephrin-A2 expression is down-regulated in the SC to a weak gradient. At 1 month after optic nerve transection, EphA5 expression is reduced in the few remaining RGCs and is no longer graded; by contrast, SC ephrin-A2 is up-regulated to a rostral(low)-caudal(high) gradient. Here we examined expression in adult rat 1 month after bridging the retina and SC with a peripheral nerve graft, a procedure that enhances RGC survival and permits RGC axon regeneration. Double labelling with cell markers revealed preservation of a nasal(low)-temporal(high) EphA5 gradient in RGCs and establishment of a rostral(low)-caudal(high) ephrin-A2 gradient within neurones of the SC. The results suggest a potential for guidance cues to restore the topography of RGC axons in the SC. However, high ephrin-A2 levels were also found in astrocytes surrounding the peripheral nerve graft insertion site. The repulsive ephrin-A2 environment offers at least a partial explanation for the observation that only a limited number of RGC axons can exit the graft to enter target central nervous system tissue.


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CRRD Object Information
CRRD ID: 2301727
Created: 2008-10-30
Species: All species
Last Modified: 2008-10-30
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.