The Eyes Have It in Nerve Regrowth

Clean-cut method of severing optic nerve may restore some sight

TUESDAY, Dec. 11, 2001 (HealthDayNews) -- Half an inch may not seem like much, but it's a giant leap forward to a German team trying to regenerate nerves.

Using severed optic nerves from rats, researchers at the University of Münster have managed to trigger the most substantial nerve regrowth ever produced.

Moreover, their technique, which involves a clean cut and reattachment of the nerve along with proteins produced by an eye injury, seems to restore some sight to the rats.

The findings, which appeared in a recent issue of Experimental Neurology, could lead to a method of treating blindness or spinal cord injuries in people. Rat optic nerves are often used as a model of the human spinal cord.

The study follows 15 years of research into how cells in the optic nerve react to cutting or crushing injuries.

Earlier studies had used forceps to crush the optic nerve, but that creates a huge scar around which a nerve's axons, or long trailing tails, struggle to grow. The new research suggests that cleanly cutting the optic nerve, then sewing the ends together, makes the axons grow together much more successfully.

"Once the scar has been formed, one has to microsurgically clean the scar again," says senior author Solon Thanos, a professor of ophthalmology at the University of Münster. "We have to cut the nerve completely to initialize growth of the fibers."

Larry Benowitz, a director of neuroscience research in neurosurgery at Children's Hospital in Boston, calls the team's clean-cut method a breakthrough.

"It's a big advance," Benowitz says. "If you surgically provide a better environment for those nerve terminals to grow through, they'll do spectacularly well."

But the clean cut isn't the whole story, the researchers discovered.

Optic nerve regrowth research has focused on introducing substances into the eye that trigger nerve growth, but this study found that nerve survival is much better following injury to the lens of the eye. Now, the researchers think they know why.

Scar tissue seems to tell the exposed end of a damaged nerve to release a protein that inhibits nerve growth. But if the lens of the eye is damaged, it releases another type of protein, called crystallins, which seem to head off this inhibitory protein.

"The stimulation of the cells by the lens injury is so critical that [nerve] axons start to grow before an inhibitory scar is formed at the site of the injury," Thanos says. "Then a secondary cascade, which we don't understand completely yet, is initiated that supports survival."

Previous studies had achieved nerve growth of between 1 and 4 millimeters, but Thanos' team managed to stimulate growth of up to 14 millimeters (0.55 inches).

The method still has limitations. For example, Benowitz cautions that nerves need to regenerate according to a fairly specific "visual map" in order for the brain to produce clear images of the world. But the researchers suspect that the brain's ability to adapt to a slightly imperfect map will ultimately lead to some level of regained sight.

"We think that the quantitative regeneration that we have is sufficient [for] rudimentary vision," Thanos says. That means, he adds, that it should restore the ability to distinguish between light and dark as well as crude objects; "let's say 10 percent or 20 percent of normal visual acuity."

Thanos also says that, although doctors may never be able to restore 20/20 vision, further refinements of the technique should allow restoration of much greater visual abilities.

But because intentional injury of a patient's lens is out of the question, and because researchers want to expand these results to other nerves, like the spinal cord, the researchers are now trying to determine whether key steps in this process could be used clinically.

In future studies, Thanos says he hopes to discover the details of this mechanism, such as how the crystallin proteins are absorbed by the cells and exactly what happens during the secondary cascade that follows.

What to Do: Learn the basics about neurons from Neuroscience for Kids, or have a look at the National Eye Institute Web site for this diagram of the eye. The National Spinal Cord Injury Association has good information on spinal cord damage.

SOURCES: Interviews with Solon Thanos, Ph.D., professor, department of experimental ophthalmology, University of Münster School of Medicine, Münster, Germany; Larry I. Benowitz, Ph.D., director of neuroscience research, department of neurosurgery, Children's Hospital, Boston; Dec. 1, 2001, Experimental Neurology
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