Monday, May 15, 2006.
A protein has shown the ability to regenerate optical nerves in rat experiments.
One of the great challenges in neuroscience has been learning how to coax nerves to regenerate after injuries. Now scientists have shown that a newly discovered and highly potent growth-promoting molecule can regenerate the optic nerves of rats -- and do so days after the nerves have been damaged.
Although still in its early stages, the research offers hope that one day a treatment can be devised for people who suffer damage to the optic nerve, which connects the eye to the brain. Furthermore, the work suggests that this growth factor may help with spinal-cord injuries as well.
Published in the journal Nature Neuroscience, the study found that rats' optic nerves were stimulated to regrow by several millimeters, says Larry Benowitz, director of the Neuroscience Laboratory at the Children's Hospital in Boston, who led the research.
The experiment involved placing a protein with previously unidentified growth-promoting properties into the eye fluid of rats whose optic nerves had been crushed three days earlier.
"This is not going to restore sight," cautions Jerry Silver, a neuroscientist at Case Western Reserve University in Cleveland. "But it has opened up a new chapter in regeneration biology." Not only does the research identify an entirely new growth-promoting molecule for nerves, which appears to be more potent than any other neurotrophic substances, says Silver, but it also explains the mechanisms involved.
The notorious reluctance of nerve fibers to heal themselves has left millions of people permanently impaired. And previous efforts to encourage these fibers to regenerate have had mixed results, says Martin Berry, a neuroscientist in the Molecular Neuroscience Group at the University of Birmingham, U.K.
Until now, the most promising regeneration had been achieved by both Benowitz and Silver independently, using an unlikely approach. "We had earlier found that when we caused an inflammatory reaction in the eye, it paradoxically stimulated nerves in the eye to go into a growth state," says Benowitz. It was known that this odd effect was likely due to a type of white blood cell, called macrophages, secreting some unknown substance.
Working with colleagues from Harvard Medical School, the University of Missouri, and MIT, Benowitz has now shown, through a painstaking process of elimination, that the protein responsible is a small molecule called oncomodulin.
The discovery was surprising because oncomodulin does not belong to a family of molecules known for promoting growth, says Benowitz. Yet tests on cultured nerve cells showed that the molecule was capable of promoting up to 50 percent more growth than known growth promoters, says Benowitz. Following this, the group was able to show that oncomodulin can regenerate the crushed optic nerve of healthy adult rats after two weeks, without the need to stimulate an inflammatory response.
"We know that it works by binding to a receptor on the surface of the nerve cells," says Benowitz. "This activates a signalling pathway that turns on a group of genes required to make nerves grow."
"He's certainly added a new tool to our arsenal," says Silver. But there's still a long way to go. Restoring sight in humans would still require the regeneration of the optic nerve several times further than was achieved in the current experiments. And first it remains to be seen if oncomodulin will have the same neurotrophic effect on humans.
The next steps are to see what effect the protein has on other types of nerve cells and if there is any danger of causing damage to other parts of the brain. Preliminary tests by Benowitz's group are hopeful, though; the oncomodulin has had some effect on nerve cells other those in the optic nerve. And that, says Berry at the University of Birmingham, "has implications for spinal-cord regeneration."
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