Harvard Medicine

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Getting the Nerve

Photo credit: iStockphoto.comWhen it comes to cellular regeneration, nerve cells, especially those in the brain, present a singular challenge. So it’s significant news that HMS researchers at Boston Children’s Hospital have managed to not only regrow some optic-nerve fibers, but also to re-establish some level of vision in mice with severe optic-nerve damage. The study, by a team led by Larry Benowitz, an HMS professor of surgery and director of Laboratories for Neuroscience Research in Neurosurgery at Children’s, is the first of its kind to show that regenerated fibers can regrow to span the distance from eye to brain, can connect with the brain’s visual centers and form synapses with other neurons involved in deciphering visual impulses, and can become wrapped in myelin, the material that helps speed the transmission of nerve impulses.

Building on several years of research, the team used a three-pronged approach to regrow axons arising from retinal ganglion cells. The stepwise approach required the scientists to first stimulate the ganglion cells with oncomodulin, a growth-promoting compound discovered in Benowitz’s lab, that is secreted by cells of the innate immune system, and then to elevate the level of the signaling molecule cyclic adenosine monophosphate. For the third step, the team deleted the gene that encodes a certain cell growth–inhibiting enzyme. When these three interventions were applied to mice with damaged optic nerves, nerve fibers regrew the full length of the optic nerve and then to the brain, forming synaptic connections in appropriate visual processing centers.

The team also observed that this regeneration led to improvements in visual function; specifically, improved depth and movement detection and an increased awareness of light and dark. However, the actual vision regained by the mice was limited, and their ability to distinguish objects remained impaired. The results of this study not only show that the mature visual pathway has a greater degree of regenerative potential than anticipated, they also hold promise for people suffering from optic-nerve damage resulting from trauma or glaucoma.

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