Mouse Study Hints at Hope Against Blindness

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Researchers report they have regenerated parts of damaged optic nerves in a handful of blind mice, a breakthrough that might lead to a human cure for glaucoma and other nerve-related blindness.

A combination of gene therapy and visual stimulation prompted partial regrowth of the optic nerves, restoring some communication between the brain and the eye in these mice, said study senior researcher Andrew Huberman.

“We didn’t regenerate every cell from the eye to the brain,” said Huberman, an associate professor of neurobiology at Stanford University School of Medicine, in Palo Alto, Calif. “It was a small fraction of the total number of cells.

“Nonetheless,” he added, “the mice could use that limited number of regenerated cells to see certain things. They went from being blind mice to being mice that could see a number of things.”

Nerve cells attached to the central nervous system normally do not regenerate, Huberman said. People blinded by glaucoma — in which increasing eye pressure damages the optic nerve — never regain the sight they lost.

Eye doctors typically put all their effort into preventing further loss of vision in people with glaucoma, said Dr. Andrew Iwach, chair of the Glaucoma Research Foundation.

“This data shows that there is a bridge to get to the other side of this, to go from being on defense to being on offense, where we can help people see,” said Iwach, an associate clinical professor of ophthalmology at the University of California, San Francisco. “That would be a game-changer for many patients.”

But Dr. Harry Quigley, director of the Glaucoma Center at the Johns Hopkins’ Wilmer Eye Institute in Baltimore, warned that people blinded due to nerve damage should not get their hopes up for an impending cure based on these results.

“It isn’t anything that could be turned into therapy in a human anytime soon, and I don’t think they’re suggesting that,” Quigley said.

For this study, Huberman and his colleagues used forceps to crush the optic nerve leading to one eye in a group of laboratory mice. They then set about trying to repair the nerve they’d damaged, using different therapies.

Simply regrowing the connection between the eye and the brain wasn’t enough — the researchers also had to make sure that the connection would rewire itself correctly. “If neurons don’t wire up correctly, you get failures of the brain to function properly,” Huberman explained.

Partial regeneration of the optic nerve occurred when researchers used gene therapy to stimulate the mTOR pathway, a process in the body that promotes growth of nerve tissue.

The research team also had some success in promoting optic nerve regeneration through visual stimulation. Placed in a “mouse IMAX theater,” the mice used only their damaged eye to watch a series of high-contrast moving bars. That therapy promoted some nerve regrowth, the researchers said.

But neither approach alone could re-establish the link between brain and eye. “We found that the neurons would regrow, but not very far,” Huberman said. “They would grow towards the brain, but they couldn’t reconnect with the brain.”

However, combining both gene therapy and visual stimulation caused a small part of the optic nerve to fully regenerate a connection between the eye and the brain, the researchers found.

“When we did that, we saw an incredible synergistic effect,” Huberman said. “The axons not only regrew, but they grew very fast and they regrew all the way back into the brain.”

Vision tests performed after the therapy showed that the connection had wired up properly.

One test projected an expanding dark circle onto the damaged eye, meant to give the impression of a bird of prey’s approach. The mice responded to the stimulation, scrambling for shelter to avoid the threat.

Huberman hopes to begin human experiments soon. “We are going directly from this into human studies,” he said. “We’re very quickly trying to move this towards technology that would allow stimulation of neurons, to test whether that would enhance regeneration.”

However, curing glaucoma-created blindness in a human will be much more complex than partially restoring sight in lab mice, Quigley said. Research with animals often doesn’t pan out in humans.

And Quigley noted that the optic nerve sustains chronic long-term damage from glaucoma, which presents a much messier problem than that faced by the lab mice.

The experiment “is not a model of glaucoma. This is a model of optic nerve injury by crushing,” Quigley explained. “Glaucoma is not as clean and easy as crushing the nerve, which is quick and dirty and all the nerve cells die at once.”

In addition, the researchers destroyed 50,000 optic nerve cells in the mice, but only were able to regenerate about 200, he noted.

“Would that really give rise to a functional improvement over blindness?” Quigley asked. “There’s no question you can do something to improve the regrowth of some few nerve cells in the eye. The difficulty is that for the many, many people who have eye diseases who are already visually impaired or blind, they’re going to think, ‘Oh, great! This is a treatment that’s going to help me.’ “

The study findings were published online July 11 in the journal Nature Neuroscience.

More information

For more on glaucoma, visit the U.S. National Eye Institute.

Source: HealthDay

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