• Optic Nerve Can Be Partially Regrown in Mice, May Lead to Human Therapies

    Written By: Celia Vimont
    Aug. 30, 2016

    A recent study has found that parts of damaged optic nerves in blind mice can be regrown. This research may have implications for the treatment of glaucoma and other degenerative retinal diseases in humans, according to experts. The optic nerve becomes injured when a person develops glaucoma.

    Researchers used a combination of gene therapy and visual stimulation to trigger partial regrowth of the optic nerve, the part of the eye that carries visual information to the brain. Regrowing optic nerves restored some communication between the eye and the brain in the mice. The study is published online in Nature Neuroscience.

    "We didn't regenerate every cell from the eye to the brain," study senior researcher Andrew Huberman, PhD, of Stanford University’s School of Medicine told HealthDay. "It was a small fraction of the total number of cells. … They went from being blind mice to being mice that could see a number of things."

    Andrew Iwach, MD, chair of the Glaucoma Research Foundation, which contributed funding to the new study, told the American Academy of Ophthalmology: “When the optic nerve is damaged by eye pressure in glaucoma, we can slow down or halt the progression of the disease, but we can’t restore the nerve fibers. Being able to restore some of these fibers would be revolutionary in terms of treatment.”

    “What had been impossible has become at least possible in an animal model,” said Dr. Iwach, who is also associate clinical professor of ophthalmology at the University of California, San Francisco. “This study shows us that we can go from only doing defense in treating glaucoma to doing offense. We still need to do a lot of research to understand what the potential could be in humans. We’re not there yet, but there is great hope.”

    In previous research, the scientists had found increasing activity of a protein called mTOR prompted regrowth of optic nerve cells. In the study, Dr. Huberman and colleagues used gene therapy to cause the retinal cells of mice to make extra copies of mTOR. Two weeks later, the researchers caused optic nerve damage in one group of mice. For visual stimulation, the mice then were put into a chamber where they looked at high-contrast changing patterns of black lines.

    These mice had modest but significant regrowth of the optic nerves, compared with a second group of mice that did not have this high-contrast visual stimulation. The nerve cells grew toward the brain, but not far enough to reconnect with the brain.

    In a third group of mice, the researchers stimulated mTOR activity, and then sutured shut the mice’s undamaged eye. This forced the mice to use the injured eye when they looked at the changing black lines. This treatment prompted regrowth down the entire length of the optic nerve and into visual centers in the brain. Visual tests conducted after the treatment ended showed the mice regained limited vision.

    In three weeks, the optic nerve cells grew at a rate about 500 times faster than untreated optic nerve cells. The study answered the question of whether a nerve cell that regenerates finds its way back to the correct brain area, instead of wandering, Huberman noted in a news release from the National Eye Institute (NEI), which partially funded the study. However, only about 1 to 5 percent of the optic nerve cells regenerated.

    “This study’s striking finding that activity promotes nerve regrowth holds great promise for therapies aimed at degenerative retinal diseases,” said Thomas Greenwell, NEI Program Director for Retinal Neuroscience Research. Retinal degenerative diseases include age-related macular degeneration and retinitis pigmentosa.

    Dr. Huberman’s team is now working with ophthalmologists and virtual reality experts to develop visual stimulation interventions to encourage optic nerve cell regrowth in people with eye disease or injury. They do not plan to try mTOR treatment in humans at this time, because it is risky and invasive, Dr. Huberman told The New Scientist.

    Until a treatment is developed that can restore nerve fibers damaged by glaucoma, it is essential to get screened for the disease as early as possible, Dr. Iwach said. He noted that while glaucoma damage cannot be reversed, blindness from the disease often can be prevented with early treatment. Glaucoma often does not produce any symptoms in the early stages, so many people with the disease do not know they have it. A complete eye exam is the only sure way to diagnose glaucoma.

    To talk to a doctor about your vision, find an ophthalmologist near you.