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EphA5 and ephrin‐A2 expression during optic nerve regeneration: a ‘two‐edged sword’
Author(s) -
Symonds A. C. E.,
King C. E.,
Bartlett C. A.,
Sauvé Y.,
Lund R. D.,
Beazley L. D.,
Dunlop S. A.,
Rodger J.
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05321.x
Subject(s) - optic nerve , biology , ephrin , neuroscience , axon , superior colliculus , anatomy , retina , ganglion , microbiology and biotechnology , signal transduction
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.