MAR 15, 2018 9:00 AM PDT

Axon Regeneration in the CNS: Insights from the Optic Nerve

Presented at: Neuroscience 2018
C.E. Credits: P.A.C.E. CE Florida CE
Speakers
  • Professor of Neurosurgery and Ophthalmology, Harvard Medical School, Neurosurgical Innovation and Research Endowed Professor, Boston Children's Hospital
    Biography
      Larry Benowitz holds the Neurosurgical Innovation and Research Professorship at Boston Children's Hospital, and is a Professor of Neurosurgery and Ophthalmology at Harvard Medical School. Larry received his PhD from Caltech with Nobel Laureate Roger Sperry and did postdoctoral fellowships at MIT and Harvard Medical School before joining the Harvard faculty, where he has worked for many years studying plasticity and regeneration of CNS connections, with a particular emphasis on the regeneration of the optic nerve. In the past decade, his group has studied the role of inflammation, oncomodulin and the protein kinase Mst3b in optic nerve regeneration, the role of TNF-alpha in animal models of glaucoma, the role of inosine in rewiring neural connections after stroke and spinal cord injury, combinatorial therapies to promote the rewiring of connections between the eye and the brain, and most recently, the role of zinc dysregulation and intra-retinal communication networks in controlling outcome after optic nerve injury. Dr. Benowitz has mentored many students and postdoctoral fellows and is first- or senior author on over 150 papers, reviews and book chapters. He was named by Scientific American as one of the 50 leaders of the year in science and technology in 2006, and more recently was awarded the Lewis Rudin Prize for "the most significant scholarly article on glaucoma published in a peer-reviewed journal in the prior calendar year".

    Abstract:

    The inability of neurons to regenerate damaged axons within the CNS has dire consequences for victims of traumatic or ischemic brain injury and multiple neurodegenerative diseases. Like other CNS pathways, the optic nerve cannot regenerate if injured and soon the retinal ganglion cells (RGCs), the projection neurons of the eye, begin to die, precluding visual recovery. Our lab and others have identified methods that enable some RGCs to regenerate axons from the eye to the brain. Some of these methods include controlled intraocular inflammation and elevation of on-comodulin and other growth factors, deletion of genes that suppress regeneration such as pten, socs3, klf4 and -9, and counteracting cell-extrinsic suppressors of axon growth by deleting re-ceptors for Nogo and other molecules{Benowitz, 2017 #5372}. Nonetheless, even under the best of circumstances, most RGCs go on to die and only a small fraction of the surviving RGCs re-generate their axons {de Lima, 2012 #4249}. These findings imply the existence of other major suppressors of RGC survival and axon regeneration. We recently identified mobile zinc (Zn2+) one such factor. Within an hour after optic nerve injury, Zn2+ increases dramatically in synaptic vesicles of amacrine cells (ACs), the inhibitory interneurons of the retina, and is then exocytosed and accumulates in injured RGCs. Zn2+ chelation leads to the persistent survival of many RGCs and to appreciable axon regeneration, with a therapeutic window of several days{Li, 2017 #5363}. Zn2+ elevation is induced by nitric oxide (NO), a gaseous signal that is generated in a small population of ACs by the enzyme NO synthase-1 (NOS1). A novel fluorescent NO sensor reveal a dramatic increase in retinal NO levels within an hour of optic nerve damage. NO or a derivative is likely to liberate Zn2+ from metallothioneins. NO also has a second, positive effect on optic nerve regeneration through a cGMP-dependent pathway. Thus, NO generated by NOS1 in a small population of ACs is responsible for the deleterious elevation of Zn2+ after optic nerve regeneration, but also exerts a positive effect on optic nerve regeneration via cGMP sig-naling. These findings, together with others in the field, are bringing us closer to improving out-come after injury to the optic nerve and are likely to have relevance to parts of the CNS.


    Show Resources
    You May Also Like
    SEP 05, 2019 4:00 PM CEST
    C.E. CREDITS
    SEP 05, 2019 4:00 PM CEST
    DATE: September 5, 2019TIME: 7:00am PT, 10:00am ET, 4:00pm CEST PCR (Polymerase Chain Reaction) has gone through a massive evolution since its development in 1983. Besides it...
    NOV 18, 2019 7:00 AM PST
    C.E. CREDITS
    NOV 18, 2019 7:00 AM PST
    DATE: November 18, 2019TIME: 7:00am PST, 11:00am EST, 4:00pm CEWT How often do you pipette in your cell culture lab every day? Usually, we do it so often that we tend stop th...
    JAN 23, 2020 9:00 AM PST
    C.E. CREDITS
    JAN 23, 2020 9:00 AM PST
    DATE: January 23, 2020 TIME: 9:00am PST, 12:00pm EST...
    OCT 02, 2019 11:00 AM PDT
    OCT 02, 2019 11:00 AM PDT
    DATE: October 2, 2019TIME: 11:00am PDT, 2:00pm EDT Ditch the Excel spreadsheets and manage your molecular workflows entirely in your LIMS Achieve configuration of molecular workf...
    NOV 07, 2019 10:00 AM PST
    C.E. CREDITS
    NOV 07, 2019 10:00 AM PST
    DATE: November 7, 2019TIME: 10:00am PST, 1:00pm EST Studying the pathogenesis of diabetes requires detailed analysis of the pancreatic islet microenvironment and its numerous c...
    MAR 24, 2020 10:00 AM PDT
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    C.E. CREDITS
    MAR 24, 2020 10:00 AM PDT
    Add to Calendar Select one of the following: iCal Google Calendar Outlook Calendar Yahoo Calendar
    DATE: March 24, 2020 TIME: 10:00 am PDT, 1:00pm EDT The Clampfit software module is a useful tool to manipulate and analyze electrophysiological data acquired by pCLAMP™ software. Rece...
    Loading Comments...
    Show Resources