Project 7

Axonal transport following partial optic nerve injury in a model of secondary degeneration: the effects of lomerizine

Secondary degeneration following head and spinal cord injury means that any surviving intact tissue is highly compromised; as a result function is severely reduced. Rescuing such intact but vulnerable tissue is currently the only feasible way to optimize function following neurotrauma. Evidence suggests that one possible way to limit secondary degeneration is to maintain axonal transport. Impaired axonal transport is already implicated in numerous pathological conditions including transient ischaemia, glaucoma and diffuse axonal injury. In this project, we will use the visual system as a model to study and potentially improve axonal transport following partial injury to the optic nerve. We generate an incomplete optic nerve injury in which the dorsal side of the optic nerve is severed and the remainder (ventral side) is left intact. Several recently reported lines of evidence have led us to deduce that calcium channel blockers are excellent candidates for improving axonal transport. We will assess the effects of the calcium channel blocker lomerizine in our model of secondary degeneration and monitor axonal transport following intraocular injection of anterograde tracers. We may also assess the effects of lomerizine on an in vitro model of secondary degeneration currently being developed. This project has the potential to deliver findings of considerable clinical relevance and is part of a multi-faceted study on secondary degeneration. As such, some flexibility in experimental scheduling and a prompt start in 2008 would be required. In addition the project requires that the student is comfortable working with animals.