Project 19

Changed cAMP activity affects the rate of retinal ganglion cell axon regrowth and transiently disrupts topography during optic nerve regeneration

Injury to the mammalian CNS results in loss of function due to neuronal death and a failure of axonal regeneration. Recent studies in rodents have suggested that increasing the levels of intracellular signalling pathways such as MAP kinase and PI3 kinase can increase survival and regeneration in the injured visual system. However, the impact on final connectivity and visual function can not be determined in these models due to the near absence of regenerated synaptic connections. To address this important question, the project will study optic nerve regeneration in goldfish, in which almost 100% of retinal ganglion cells (RGC) survive and regrow their axons to restore topography and useful vision.

We will use pharmacological agents to alter the activity of the MAP kinase and/or PI3 kinase in goldfish the goldfish visual pathways at key times during optic nerve regeneration. Survival will be assessed by counts of retinal ganglion cells. Axon regeneration will be examined by immunohistochemistry and axon tracing. Connectivity and topography of the regenerate projection will be measured electrophysiologically. Additional biochemical techniques (ELISA, kinase assays) will be used to confirm activity of the agonists and antagonists employed.

The robust regeneration and predictable timecourse in goldfish provides a unique opportunity to study the role of signalling pathways in mediating key aspects of neuronal regeneration, including survival, regeneration and connectivity.