Eyeing a cure.
Damaged nerve fibers don't regrow (top) unless treated with oncomodulin (bottom).

Credit: Larry Benowitz

By Prashant Nair
ScienceNOW Daily News
15 May 2006

The optic nerve connects the eye to the brain. Injuries or diseases such as glaucoma can damage it, and once severed, nerve fibers projecting from the retina via the optic nerve don't regrow. In the past, scientists have achieved modest sprouting of these neurons in rats by inducing an inflammatory reaction in the eye. But here's the rub: The macrophages that spark the sprouting also spew toxic chemicals, which can kill nerve cells.

So neurobiologists led by Larry Benowitz at Harvard Medical School sought to separate the helpful component of macrophages. By looking at various substances secreted by macrophages in culture, the team isolated a protein called oncomodulin that seemed to promote regrowth and elongation of optic axons--fine, spidery extensions of the nerve cells--without the toxic side effects seen with the entire cells. When added to nerve fibers grown in dishes, the protein caused the axons to grow by nearly 45%--a 50% improvement over other growth stimulants.

The effect in live animals was also dramatic. When the team injected oncomodulin into the fluid between the lens and the retina of rats whose optic nerve had been crushed, most of the animals experienced 7-fold greater regeneration of their optic nerve neurons than untreated rats. No other growth stimulants have been able to induce this much regeneration in rats, the researchers reported online yesterday in Nature Neuroscience.

Despite the success, the team was unable to restore vision in the rats, and the strategy still has a ways to go before it can be applied to humans. First, says Benowitz, researchers must overcome the enormous hurdle of getting the axons from the retina to connect to the appropriate places in the brain.

Still, the technique is promising, says Jerry Silver, a neuroscientist at Case Western Reserve University in Cleveland, Ohio, because the treatment was done 3 days after injury. Most delayed treatments induce severe inflammation, he says, so the identification of a safer molecule is an important step. And neurobiologist Dongfeng Chen of the Schepens Eye Research Institute in Boston, Massachusetts, says the approach could also extend beyond optic nerve regeneration: One day, she says, it may also be used to treat spinal cord injury.