In Nature Neuroscience, a team led by senior author Andrew Huberman, an associate professor of neurobiology who heads a neural vision lab at Stanford University School of Medicine in California, reports unprecedented success in restoring broken links between retinal ganglion cells and various parts of the brain in mice.
The researchers describe how they coaxed optic-nerve cables that carry vision information from the eye to the brain, to regenerate. They found the cables not only repaired themselves, but also re-traced the same routes they had before being severed.
Before the scientists regrew the connections, the mice's condition was similar to glaucoma, a major cause of blindness where pressure in the eye impairs the function of the optic nerve.
Prof. Huberman explains that while you can restore vision in people with cataracts - the leading cause of blindness - by removing the clouded lens, there are as yet no vision-restoring treatments for people who lose their sight through glaucoma.
There are around 70 million people worldwide with glaucoma. Damage to the optic nerve can also occur through other ways, such as injury, retinal detachment, tumors in the pituitary gland, and brain cancer.
High-contrast exposure and biochemical manipulation
When we look at something, light that bounces off the object enters our eye, is focused onto the retina by our lens and/or glasses, and is picked up by photoreceptor cells on the retina - a thin sheet of cells at the back of the eye.
Fast facts about glaucoma
- The number of Americans with glaucoma is expected to reach6.3 million in 2050, nearly double the 2010 figure
- Glaucoma is more common in older people
- It is twice as common in African Americans than in whites or Hispanics.
Find out more about glaucoma
The photoreceptor cells pass coded information to another set of cells called retinal ganglion cells. The ganglion cells project long, thin fibers called axons, which fan out - at the other end of the optic nerve - to various parts of the brain, where they connect with other nerve cells to build the picture that we "see."
There are around 30 types of retinal ganglion cells, each dealing with a particular aspect of vision, such as motion in general, motion up or to the side, and colors.
Prof. Huberman says somehow the brain interprets this bundle of signals to be aware, and say, for example: "Wow, that's a fast-moving car coming my way - I'd better get back on the sidewalk."
He explains that the retinal ganglion cells send signals to over two dozen areas of the brain, involved in processing of not only what we would class as vision, but also mood and circadian rhythm.
However, while over a third of the brain is dedicated to processing vision-related information, retinal ganglion cells are the only cells that connect the eye to the brain, he notes, and adds:
"When those cells' axons are severed, it's like pulling the vision plug right out of the outlet."
The team found they could induce the severed optic nerve in mice to regenerate by treating them with a daily regimen of intensive exposure to high-contrast images, or biochemical manipulation that kicked a pathway in the retinal ganglion cells back into high gear, or both.
The pathway is called mTOR, and is already known for playing an important role in the developing brain. When this path slows down or is lost - as happens in the adult brain - a cascade of growth-promoting molecular interactions shuts down with it.
The researchers tested the mice's vision after 3 weeks of treatment and examined their brains to see if any axons had regenerated.
Both parts of treatment necessary
An important observation was that while the axons of the ganglion cells are destroyed when the optic nerve is severed, the photoreceptor cells, and their links to the ganglion cells, remain intact.
The researchers found if the mice received only one of the two parts of the treatment - either the visual stimulation or kickstarting the mTOR pathway - it did not work. It was the combination of the two that caused substantial numbers of axons to regrow and migrate into the appropriate destinations of the brain.
Another important observation was that the axons retraced their original routes, Prof. Huberman says, it is as though the cells "retained their own GPS systems. They went to the right places, and they did not go to the wrong places."
The team found that while the treatment was successful - they tested mice who had only one damaged eye, and covered the good eye while the mice went through different challenges - some parts of vision were still missing.
The parts of vision responsible for fine discrimination were still not working. The team could prove axons from two specific retinal ganglion cell types reached their targets, but they lacked the molecular tags that tell them if axons from other relevant cells had done so.
The team is already working on improving the treatment.
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