In a groundbreaking series of experiments, scientists from the Stanford University School of Medicine and their colleagues have successfully restored several essential aspects of vision in mammals for the first time – work that would eventually help restore sight to the blind.
Their research, which was detailed in a paper published online Monday in the journal Nature Neuroscience, involved coaxing severed optic nerve cables to regenerate.
As they did so, senior author Dr. Andrew Huberman, an associate professor of neurobiology at Stanford, and his colleagues found that they nerves could retrace their previous routes and were able to re-establish connections with the necessary parts of the brain.
Prior to the procedure, the mice had a condition similar to glaucoma, one of the primary causes of blindness in humans. Glaucoma affects nearly 70 million people worldwide, the study authors said in a statement, and is caused when there is too much pressure on the optic nerve. Their new findings could potentially help reverse vision loss causes by this disease, they noted.
Coaxing retinal ganglion cell axons to regenerate
Among the essential components required for humans and other mammals to be able to see are the retinal ganglion cells (RGCs), which are a type of neurons that produce long, slender, wire-like processes known as axons. Bundles of axons extend down the length of the optic nerve and then fan out to connect with nerve cells in the brain.
The axons pass along electrical signals that contain information about what is being seen. Those cues are then interpreted by the brain, the researchers explained. More than two dozen regions of the brain receive signals from RGCs, which are the only nerve cells that connect it to the eye. If the connection is severed, “it’s like pulling the vision plug right out of the outlet,” Dr. Huberman explained, and in mammal brains, damaged axons typically do not regenerate in mammals.
As a result, damage to the RGC axons in mammals typically equals permanent loss of vision, the study authors said. However, in most cases, axons located outside of a mammal’s central nervous system are able to regenerate, and during the early stages of development, nerve cells often grow and generate new axons in the brain and spinal cord – cells that can somehow navigate their way through bundles of brain tissues to reach their desired targets within the mammalian brain.
Adult brain cells lose the capacity to regenerate over time because an intracellular pathway that encourages growth known as the mTOR pathway becomes less active in these cells. In their new study, Dr. Huberman’s team treated mice which had a damaged optic nerve in one eye with either a regimen of daily exposure to high-contrast visual stimulation (images of a moving black-and-white grid), biochemical manipulations which caused the mTOR pathway to become more active, or a combination of the two treatment methods.
The mice were then tested three weeks later, and the researchers discovered that both the mTOR-pathway reactivation and the visual stimulation resulted in modest regrowth of RGC axions, but only to the point of the optic chaiams, where healthy axons leave the optic nerve and begin to go to other parts of the brain. However, the combination of the two approaches caused a substantial number of axons to grow, move beyond the optic chasm, and spread throughout the brain.
While vision was successfully restored, the process is not perfect
The study authors went on to test the vision of the mice, and found that the RGCs were receiving visual input from the damaged eye’s photoreceptor cells and conveying it to the correct areas of the brain . In fact, in one test that simulated the approach of a bird of prey, the eye that had been damaged spotted the predator and the mice took appropriate action.
“Somehow these retinal ganglion cells’ axons retained their own GPS systems. They went to the right places, and they did not go to the wrong places,” Dr. Huberman explained in a statement. In short, the regenerating axons were able to grow, reach the various parts of the brain and managed to re-establish functional links with those areas to effectively restore vision in a once blind eye.
However, the researchers emphasize that the eye was not exactly as good as new. On some tests that required detailed visual discrimination, the mice failed. They pointed out that the axons from a pair of specific RGCs reached their targets, but lacked the molecular labels that would have let them known whether or not axons from other subtypes had done likewise.
Solving this issue will require the scientists to increase the total number of ganglion cell axons that successfully reach and re-establish contact with the correct part of the brain, and to discover some way to engage and assess a greater number of the nearly 30 RGC subtypes, Dr. Huberman, who worked on the study with researchers from the University of California-San Diego, Harvard University and Utah State University, noted. “We’re working on that now,” he added.
Image credit: Thinkstock