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Pufferfish Toxin Holds Clues To Treating 'Lazy Eye' In Adults

Updated September 15, 2021 at 1:15 PM ET

A treatment that simulates the loss of an eye may help adults with the vision impairment known as amblyopia or "lazy eye."

Studies in mice and cats suggest that the approach allows the brain to rewire in a way that restores normal vision, a team reports this week in the journal eLife.

"It's as if you've turned back the clock to a period of early development," says Mark Bear, Picower professor of neuroscience at MIT, and coauthor of the study.

The result is likely to make other scientists "start to rethink what sort of visual experience can retrain the visual system in adulthood," says Steven Grieco, a postdoctoral fellow in anatomy and neurobiology at the University of California, Irvine.

Why the childhood treatment isn't enough

Amblyopia, which occurs when the brain starts ignoring the signals from one eye, is typically treated during childhood with a patch, special glasses, or eye drops. The idea with that approach is to restrict use of the strong eye, forcing the brain to form stronger connections with the weak eye.

But the strategy has limits.

"There are a very significant number of adults with amblyopia where the treatment either didn't work, or it was initiated too late," Bear says.

After a critical period that ends at about age 10, the connections between eye and brain become less malleable, losing what scientists call plasticity.

So for several decades, Bear and a team of researchers have been asking: "How can we rejuvenate these connections? How can they be brought back online?"

To find out, Bear's team studied adults with amblyopia who lost their strong eye because of a disease or injury.

"Unexpectedly, in many cases vision recovered in the amblyopic eye," Bear says, "showing that that plasticity could be restored even in the adult."

Next, the team did an experiment with mice and cats.

"A fantastic example of the brain's plasticity as we age"

They injected an animal's good eye with tetrodotoxin, a paralyzing nerve toxin found in fugu, a type of puffer fish. The toxin is so powerful that fugu sashimi can be lethal if prepared incorrectly.

But when a tiny amount is injected into an eye, it blocks all communication with the brain. "So we simulate loss of the eye, but only temporarily — only for a matter of day or two," Bear says.

That's long enough to set the stage for rapid change in the brain's wiring, he says. When the toxin wears off, the brain begins making new connections with the amblyopic eye and the animal's vision improves.

The study is "a fantastic example of the brain's plasticity as we age," says Jennifer Raymond, Berthold and Belle N. Guggenhime professor of neurobiology at Stanford University.

The finding is the latest evidence that amblyopia can be corrected in adults. The next step will be to test the approach in primates, Bear says.

In the meantime, researchers are trying other tactics to treat amblyopia in adult brains.

Grieco is part of a team at the University of California, Irvine, that has done experiments using the drug ketamine, which is thought to induce plasticity throughout the brain.

"Mice that were treated with ketamine, the vision in their amblyopic eye improved very significantly," Grieco says.

The treated mice spotted a visual target that the other mice couldn't see, Grieco and his team reported in 2020 in the journal Current Biology.

Even without drugs, adult brains retain the ability to rewire, if pushed, Raymond says.

"I learned to surf a couple of weeks ago at an age where I thought maybe it was too late," she says. "I did learn, but not as fast as my teenagers."

That makes sense because an adult brain emphasizes retaining old skills over mastering new ones, Raymond says. But studies of adults who've had a stroke shows how much brain plasticity remains throughout life, she says.

"Often patients can recover a lot of function, whether it's movement, whether it's reading," she says. "The key question that labs like mine are asking is, how do we better enhance that plasticity?"

Answering that question, Raymond says, could have implications for education, rehabilitation, and the treatment of brain disorders. Copyright 2021 NPR. To see more, visit https://www.npr.org.

Transcript:

MARY LOUISE KELLY, HOST:

Children who develop the visual impairment often called lazy eye can be treated by covering their other eye with a patch. Now researchers think they have found a way to treat adults using a toxin found in deadly puffer fish. The approach has only been tried in animals so far, but NPR's Jon Hamilton reports the results are encouraging.

JON HAMILTON, BYLINE: A lazy eye isn't really lazy. The term refers to amblyopia, a medical condition that occurs when the brain starts ignoring the signals from one eye. Existing treatments restrict use of the strong eye in order to force the brain to pay attention to the weak one. But Mark Bear, a neuroscientist at MIT, says that approach has limits.

MARK BEAR: There are a very significant number of adults with amblyopia where the treatment either didn't work or it was initiated too late.

HAMILTON: After a critical period that ends at about age 10, the connections between eye and brain become less malleable. They lose what scientists call plasticity. So for several decades, Bear and a team of researchers have been trying to answer a question.

BEAR: How can we rejuvenate these connections? How can they be brought back online?

HAMILTON: To find out, Bear's team studied adults with amblyopia who lost their strong eye to a disease or an injury.

BEAR: Unexpectedly, in many cases, vision recovered in the amblyopic eye, showing that that plasticity could be restored even in the adult.

HAMILTON: So the team did an experiment with mice and cats. They injected an animal's good eye with the paralyzing nerve toxin found in fugu, a type of pufferfish. The toxin is so powerful that fugu sashimi can be lethal if prepared incorrectly. But Bear says when a tiny amount is injected into an eye, it blocks all communication with the brain.

BEAR: So we simulate loss of the eye but only temporarily, only for a matter of a day or two.

HAMILTON: Bear says that's enough to set the stage for rapid change in the brain's wiring.

BEAR: The brain is now in a mode where it's seeking input, and it's as if you turned back the clock to a period of early development.

HAMILTON: When the toxin wears off, the brain begins making new connections with the amblyopic eye, and the animal's vision improves. The finding, published in the journal "eLife," is the latest evidence that amblyopia can be corrected in adults. The next step will be to test the approach in primates. In the meantime, scientists are trying other tactics to treat amblyopia in adult brains. Steven Greco is part of a team at the University of California Irvine that has done experiments using the drug ketamine.

STEVEN GRECO: Mice that were treated with ketamine - the vision in their amblyopic eye had improved very significantly, and we were able to see that with behavioral testing of visual performance.

HAMILTON: The treated mice spotted a visual target that the other mice couldn't see. Greco says ketamine probably worked because it induces brain plasticity. Jennifer Raymond, a neurobiologist at Stanford University, says all of this research shows that adult brains can rewire if pushed.

JENNIFER RAYMOND: I learned to surf a couple of weeks ago at an age where I thought maybe it was too late (laughter). I did learn but not as fast as my teenagers.

HAMILTON: Raymond says that makes sense because an adult brain emphasizes retaining old skills over mastering new ones. Even so, she says, studies of adults who've had a stroke showed that the brain retains a remarkable ability to change when it needs to.

RAYMOND: Often, patients can recover a lot of function, whether it's movement, whether it's reading. But a key question that labs like mine are asking is, how do we better enhance that plasticity?

HAMILTON: Raymond says answering that question could change education, rehabilitation and the treatment of brain disorders.

Jon Hamilton, NPR News.

(SOUNDBITE OF EMANCIPATOR'S "RATTLESNAKES") Transcript provided by NPR, Copyright NPR.