Eye for growth: new protein prompts optic nerve regrowth.

A protein recently isolated from white blood cells could offer a new way to repair nerve cells damaged by injury or disease.

Like most neurons in the central nervous system, those that form the bundle that connects each eye to the brain don't regrow their long, spindly axons, which carry electrical signals, if they become injured. Since this bundle, called the optic nerve, is more accessible than are nerves inside the skull or spine, scientists have long used it as a model to investigate why other damaged nerves don't regenerate.

While experimenting on optic nerves in rats, Larry Benowitz of Children's Hospital in Boston and his colleagues discovered by accident that scratching or poking the lens in an animal's eye could prompt damaged neurons to regrow axons farther toward the brain than researchers had ever seen. The scientists eventually discovered that white blood cells called macrophages, which rushed in immediately following the lens injury, were responsible for this effect.

Other researchers' studies had shown that macrophages leach toxic chemicals that can kill nerve cells. Therefore, Benowitz and his team sought to isolate the axon-growing chemical.

The team started by collecting proteins secreted by the white blood cells, then testing how well each protein stimulated growth of crushed or severed axons. One protein, called oncomodulin, seemed to be responsible for most of the regenerative effects.

"We were baffled at first because nothing about this protein suggests it would be responsible for stimulating growth" says Benowitz. He points out that researchers have found oncomodulin in some tumor cells but haven't tied it to any known function.

Other proteins, broadly known as neurotrophic factors, stimulate some axon growth. In lab-dish experiments, axons of nerve cells treated with oncomodulin grew significantly more than did those treated with other growth-promoting proteins, Benowitz and his team report.

The scientists then tested their new protein in live rats whose optic nerves had been crushed. Benowitz' team injected the animals' eyes with oncomodulin in slow-release capsules, along with a chemical called cyclic adenosine monophosphate that's known to prompt nerve cells to respond to other growth factors. After several days, the rats' optic nerve axons showed five to seven times as much regrowth as did axons in animals that hadn't received the protein.

Benowitz and his colleagues report these results in an upcoming Nature Neuroscience. Benowitz' lab was "one of the first ones to demonstrate that macrophages promote very striking axon regeneration,' says neural-regeneration researcher Adriana Di Polo of the University of Montreal. "The fact that he's pursued the story, stuck with it, and actually identified the protein that macrophages secrete that's involved in axon regeneration is very exciting."

Even with the knowledge of this new growth factor, Alexander Ball of McMaster University in Hamilton, Ontario, notes that completely regenerating damaged axons to their preinjury state is a "tall order." He adds that researchers still need to figure out how to steer regenerating nerves to reconnect to the right targets.