Leonard Levin, MD, PhD
Monday - Friday, 8 am - 5 pm
Madison, WI 53792-0001
Departments of Neurology and Neurological Surgery.
A.B. 1980, Harvard University
Retinal ganglion cell (RGC) death is the final common pathway for virtually all optic neuropathies. The initial insult in most optic nerve diseases is injury to the RGC axon, from either ischemia, inflammation, transection, or deformation. Optic nerve injury results in RGC apoptosis, partly by interfering with retrograde transport of target-derived neurotrophic factors. Given that (1) axotomy induces RGC apoptosis and (2) most optic neuropathies are associated with initial axonal damage and subsequent RGC loss, RGC axotomy is an experimental model for understanding the pathophysiology of certain optic neuropathies. Our overall goal is to ascertain the molecular changes that occur within the RGC after axotomy, particularly those leading to induction of the apoptosis cascade, as well as hypothetical protective mechanisms. Our working hypothesis is that one of the critical molecular events underlying RGC death after axonal injury is generation of reactive oxygen species (ROS), similar to what occurs in a variety of neuronal cells. We hope to find ways of preventing RGC death from axonal injury by modulating these mechanisms.
Almost all optic neuropathies involve RGC axonal injury, except for a few disorders where the locus of injury is unknown. If ROS generation is essential for RGC death after axotomy, then this could serve as a critical point for therapeutic intervention. An understanding the molecular response of the RGC to axonal injury would be applicable to a wide variety of diseases of the optic nerve, independent of the mechanism by which the nerve is injured. As many of these diseases have no effective therapy, determination of the regulation of cell destructive and protective mechanisms could lead to innovative methods for their treatment.