3-D view of retinal ganglion cell. (National Institutes of Health)
Scientists at Stanford university have restored partial vision to mice whose optic nerves were damaged.
The researchers say the experiment, published this week in the journal Nature Neuroscience, is the first time "multiple key aspects of vision" have been restored in a mammal.
The implication of the research is that people who are completely blind due to glaucoma, tumors, or other conditions that damage the optic nerve may be able to regain some vision.
The team will next test out noninvasive ways of achieving the same result in humans, says Dr. Andrew Huberman, an associate professor of neurobiology at Stanford University and a co-author of the study.
But even in a best-case scenario, in which researchers can replicate the results in humans, any benefit is at least 10 years away, says Dr. Andrew Iwach, chairman of the board for the Glaucoma Research Foundation, a study co-funder.
The vast majority of an estimated 3 million Americans with glaucoma do not go blind, but the foundation says it is still the second-leading cause of blindness, after cataracts. In the U.S., more than 120,000 people have lost their sight due to the disease.
The mice had limited vision restored. Translating the improvement into human terms, Huberman described their visual capacity as tantamount to an individual being able to walk through a room without bumping into objects or people, or, perhaps, dodge traffic.
"There is some recovery of important functions," he says, "but not the kind of things that would be involved in reaching out for a pen on a table or texting or reading fine print."
The mouses' vision is still being monitored, and it may improve over time, Huberman says. "The brain is really good at plasticity."
Regeneration of Brain Cells
The scientists were able to partially restore vision in the mice by regenerating, in the retina, extensions called axons on the ends of cells called ganglia. These cells receive visual information and send it to the brain through the axons.
In glaucoma, retinal cells constrict from pressure, and the axons attached to them "pull out of the brain," says Huberman. When this occurs, the affected cells cannot pass the visual information on to the brain.
The researchers started the experiment by injecting the first of three groups of mice with a virus that carried a gene called mTOR, which shifted the retinal ganglion cells into a state of growth.
"Think of this kind of like steroids or exercise for retinal ganglion cells," Huberman says.
The researchers then induced an injury in the optic nerves of the mice -- an injury similar to the damage caused by glaucoma. The mTOR gene then prompted the axons to regenerate down the optic nerve, but they not all the way into the brain -- so no vision-enabling connection was made.
In the second group of mice, the researchers damaged the optic nerve without injecting the gene that triggers axon growth. Instead, the mice were treated with daily visual stimulation.
"The animals were placed in kind of an IMAX theater, where they viewed movies of high-contrast, black-and-white bars moving around," Huberman says, adding that's a visual pattern good for stimulating electrical activity of retinal ganglia.
The third and luckiest group of mice received both the gene injection and the visual stimulation. The results, Huberman says, were "spectacular."
"What we found was there was this enormous synergistic effect. The axons grew 500 times farther and faster than they would with either condition alone. And they grew so far and so fast, in fact, that they managed to get back into the brain."
The Right Wiring
Huberman says the most important question answered in the study was whether neurons -- in this case, the retinal ganglion cells that convey visual information to the brain -- would make the proper connections when regenerated. If not, "it might be worse to have the wrong regeneration than no regeneration at all."
There are 30 types of retinal ganglion cells, he says, connecting their axons to different areas of the brain and controlling different functions.
"You could imagine it would be a very bad thing to regenerate, say, the motion-sensitive neurons to the area of the brain involved in mood. Then every time something moves through your visual field, you'd have a readjustment of your mood."
But these misroutings didn't occur.
"So what this means is, if you kickstart one of these cells into a regenerative state, once they get into the milieu in which they have to figure out which way to go, they remember it like a city they grew up in, and they go to the right place."
Dr. Iwach of the Glaucoma Research Foundation said the findings were "preliminary, but very exciting."
"We currently manage glaucoma by lowering eye pressure and trying to save what is left," he says. "We have not had the ability to regenerate these connections in humans. If you lose them, your vision cannot be brought back."
"I'm hopeful," Iwach says. "I'm in the middle of seeing [glaucoma] patients, and they're struggling."
Huberman says the next step for his research team is to partner with a virtual reality group at Stanford to run a human study on ways in which noninvasive approaches can stimulate specific sets of neurons to regenerate, or can enhance their growth.
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