Research Interests: The primary long-term goal of our lab is to develop new strategies to improve patient outcomes following CNS injury and neurodegenerative disease. Our emphasis is towards treatments that both preserve and regenerate damaged neurons. We use the eye as a model system to study neuronal degeneration and regeneration because it provides many unique advantages including ease of accessibility and well documented neural circuit components.
Experimental Approaches: We primarily examine the sole projection neurons connecting the retina and the brain, retinal ganglion cells (RGCs). RGCs send axons from the eye to the brain via the optic nerve, the only isolated white matter tract in the central nervous system. A major approach in the lab is to perform complete optic nerve injury, which severs all RGC axons and allows for unambiguous assessment of RGC axon regeneration. RGCs, their synaptic partners, and surrounding glia can be manipulated by viral delivery to overexpress or knockout most genetic targets. Additionally, we can deliver pharmacological agents or growth factors to the eye to test efficacy of treatments that are more clinically relevant. A current focus of the lab is to examine how the synaptic and cellular milieu in the retina responds to remote RGC axon injury, and how such responses impact RGC survival and regeneration.
Another advantage of the eye is that retinal neurons can be monitored in vivo without surgical intervention. Our lab uses multiphoton microscopy to monitor RGC responses to injury and disease. Although RGCs are all similar in that they convey visual information from the primary sensory organ of the retina to different brain regions, there are 40 or more identified RGC subtypes which all vary in characteristics like electrical activity, metabolic demands, and cellular stress capacity. Although a large proportion of RGCs die in conditions like optic nerve crush and glaucoma, RGC subtype differences have a major impact on likelihood of survival or cell death. A goal of our lab moving forward is to leverage the inherent differences in RGC responses to injury and disease conditions, to generate new strategies of cellular preservation. Our main approach to doing this is observational science. We use in vivo imaging to determine what metabolic and signaling pathways might be disparate between well surviving and dying RGC subtypes. Such data can then be used to devise logical treatment targets that manipulate identified pathways.