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The researchers injured the optic nerves of rats, then used a two-pronged approach to get the axons to regenerate. To gas up the sluggish nerve cells, Dr. Dietmar Fischer, first author of the study, caused an inflammatory reaction by deliberately injuring the lens of the eye. Though seemingly harmful, this injury actually stimulates immune cells known as macrophages to travel to the site and release growth factors. As Benowitz's lab had found previously, these growth factors activated genes in the retinal nerve cells, causing new axons to grow into the optic nerve.
To try to enhance this growth, the researchers added a gene-therapy technique. Using a modified, non-infectious virus as a carrier, they transferred a gene developed by co-investigator Zhigang He, PhD, into retinal nerve cells that effectively removed the 'braking' action of the myelin proteins - spurring production of a molecule that sopped these inhibitory proteins up before they could block growth.
'When we combined these two therapies - activating the growth program in nerve cells and overcoming the inhibitory signaling - we got very dramatic regeneration,' said Benowitz, who is also an associate professor of neurosurgery at Harvard Medical School and holds a Ph.D. in biology/psychobiology. The amount of axon regeneration wasn't enough to restore sight, but was about triple that achieved by stimulating growth factors alone, he said.
Benowitz's lab will continue working with the optic nerve in hopes of restoring vision. 'We have to fine-tune the system, and we have some ideas of how to do it,' Benowitz said. 'But then we come to another big hurdle.' That hurdle is getting the nerve fibers from the eye to hook up to the correct centers in the brain in such a way that visual images do not become scrambled. 'It's a mapping problem,' Benowitz said. 'We have to retain the proper organization of fiber projections to the brain."
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