Eph/ephrin expression in the adult rat visual system following localized retinal lesions: localized and transneuronal up‐regulation in the retina and superior colliculus

Abstract

Following unilateral optic nerve section in adult PVG hooded rat, the axon guidance cue ephrin-A2 is up-regulated in caudal but not rostral superior colliculus (SC) and the EphA5 receptor is down-regulated in axotomised retinal ganglion cells (RGCs). Changes occur bilaterally despite the retino-collicular projection being mostly crossed. Here we investigate the dynamics of Eph/ephrin expression using in situ hybridization and semi-quantitative immunohistochemistry after localized retinal lesions. Unilateral krypton laser lesions to dorso-nasal retina ablated contralaterally projecting RGCs (DN group); ventro-temporal lesions ablated contralaterally and ipsilaterally projecting RGCs (VT group). Lesions of the entire retina served as controls (Total group). Results are compared to normal animals in which tectal ephrin-A2 and retinal EphA5 are expressed, respectively, as shallow ascending rostro-caudal and naso-temporal gradients. In both SCs of DN and Total groups, tectal ephrin-A2 was up-regulated caudally; in the VT group, expression remained normal bilaterally. Unilateral collicular ablation indicated that bilateral changes in ephrin-A2 expression are mediated via intercollicular pathways. EphA5 expression in the VT group was elevated in the intact nasal region of experimental retinae. For each experimental group, EphA5 expression was also elevated in nasal retina of the opposite eye, resulting in uniform expression across the naso-temporal axis. Up-regulation of ephrin-A2 in caudal, but not rostral, SC suggests the enhancement of developmental positional information as a result of injury. Bilateral increases in retinal EphA5 expression demonstrate that signals for up-regulation operate interocularly. The study demonstrates that signals regulating guidance cue expression are both localized and relayed transneuronally.

Functional Topography and Integration of the Contralateral and Ipsilateral Retinocollicular Projections ofEphrin-A−/−Mice

“…The role of ephrin-As in ordering these projections has not been investigated and their possible disruption in ephrin-A Ϫ/Ϫ mice may further contribute to disorder within and between retinal inputs (Withington and McCrossan, 1996;Tu et al, 2000;Rodger et al, 2005b).…”

Disease Gene Candidates Revealed by Expression Profiling of Retinal Ganglion Cell Development

“…In some cases, genes important for normal RGC development are expressed constitutively. For instance, as soon as they are generated by their precursor cells, RGCs express Eph receptors that are used 1-2 weeks later for topographic map formation in their targets in the superior colliculus and then continue to express these genes into adulthood (McLaughlin et al, 2003;Rodger et al, 2005). Other changes in RGC phenotypes may depend on developmental regulation of RGC gene expression.…”

Tectotectal Neurons and Projections: A Proposal to Establish a Consistent Nomenclature

“…Syka et al, 2000;Rushmore and Payne, 2003;Rodger et al, 2005) and ''intertectal'' (e.g., Waleszczyk et al, 1993, Jhaveri andHoffman-Kim, 1996). Again, these expressions are by themselves confusing, as they can be indistinctly applied to the commissural projection of the IC or the SC, as well as to the projections from the IC to the SC and vice versa.…”