Larry I. Benowitz, Ph.D.
Professor of Surgery and Ophthalmology
F.M. Kirby Neurobiology Center
Center for Life Science, Room 13-071
3 Blackfan Circle
Boston, MA 02115
CNS injury, including spinal cord damage, stroke, and certain degenerative diseases, can lead to permanent and devastating functional losses. Our primary interest is to understand how nerve cells form connections and to develop methods to promote the rewiring of neural connections after CNS damage. One major area of interest has been the regeneration of axons in the optic nerve. Retinal ganglion cells (RGCs), the projection neurons of the eye, are normally unable to regenerate injured axons, and consequently there is little visual recovery following traumatic nerve injury or degenerative diseases such as glaucoma. We discovered that regenerative failure can be partially reversed by inducing a controlled inflammatory reaction in the eye, causing neutrophils and macrophages to secrete a previously unknown growth factor that we identified as oncomodulin (Ocm). Combining Ocm with elevation of cAMP and deletion of the pten gene enables RGCs to regenerate axons from the eye all the way to the brain, where they form synapses in appropriate target areas and partially restore simple visual responses. Another interest has been the mechanisms that underlie RGC death after optic nerve damage and in animal models of glaucoma. Finally, we have also been studying the role of inosine, a naturally occurring purine nucleoside, in promoting anatomical plasticity and functional recovery after CNS damage. We discovered that inosine diffuses into neurons and activates Mst3b, a protein kinase that appears to be a key regulator of the cell-signaling pathway through which trophic factors stimulate axon growth. In vivo, we have found that inosine promotes axonal rewiring after stroke and spinal cord injury and improves functional recovery in both models. Current research is focused on developing gene-therapy methods to restore vision, understanding signal transduction pathways and transcriptional cascades that underlie regenerative growth, and evaluating the quality of regeneration in greater anatomical and functional detail, with a long-term goal of improving outcome for patients with CNS injury.
For a complete listing of publications click here.
Last Update: 11/13/2013