Eyeworld

EW NEWS & OPINION 26 November 2016 by Maxine Lipner EyeWorld Senior Contributing Writer people whose optic nerves are in- jured but not totally degenerated," he said. "For us that's exciting be- cause visual stimulation is complete- ly noninvasive." Given these results and the fact that the technology for delivering visual stimulation has become so good, investigators are moving to work in humans directly. "We are establishing protocols and setting up visual stimulation through the use of virtual reality for blind, glaucoma, and injured eye patients with and without growth-promoting mole- cules inserted into the vitreous," he said, adding that halting the pro- gression of glaucoma is his first goal. Overall, Dr. Huberman views the study as having several messag- es. "One is that the nervous system of humans, including the visual sys- tem, has a tremendous capacity to regenerate after injury, even severe injury," he said. The key is to find the right stimuli, which will come in the form of a combination of treat- ments. In addition, a noninvasive stimulation method, such as virtual reality, is going to be tremendously powerful because it is sensory rich and can be tightly controlled and is portable. It's akin to a portable eye clinic, Dr. Huberman said. "I want to encourage people to start thinking about and developing easily acces- sible, powerful tools to get out to the public for visual repair," he said, adding that he will be doing his part. "My job is not to develop the devices, but to establish the proto- cols," he said. EW Reference 1. Lim JH, et al. Neural activity promotes long-distance, target-specific regenera- tion of adult retinal axons. Nat Neurosci. 2016;19:1073–84. Editors' note: Dr. Huberman has no financial interests related to his comments. Contact information Huberman: adh1@stanford.edu and for central nervous system repair generally." A long-standing concern was that regenerated neurons would connect to the wrong parts of the brain, so that, for example, every time a person looked at something there would be an auditory response. If this were the case, the thinking was it might be better not to have any regeneration at all. Fortunately, investigators found that not only did the nerves regrow but they went to exactly the right location. "To us, this is incredible because they're completely recapit- ulating development many months, the equivalent of years in humans, after that development occurred, the equivalent of years in humans," Dr. Huberman said. "They remember their way back." Investigators also found that some, but not all, visual functions were restored when they assessed the ability of mice to navigate in cer- tain environments and to respond to a threat. Why some functions were restored and not others remains unclear. "Some neural pathways be- tween the eye and the brain might require more cells to regenerate or more time for those connections to become functional," Dr. Huberman said. In addition to restoring func- tion, this work could be important in halting loss of vision for those who are losing more of their fields every month. "There are a lot of group received mTOR gene therapy plus visual stimulation. Several weeks later, investigators looked at the connections between the eye and the brain. "We looked at it anatomically and we looked at the ability of the eye to communi- cate with the brain and drive visual perception and behavior in mice. The mice that got the visual stimula- tion had a little bit of regeneration, but not much," Dr. Huberman said. Likewise, the group that received the mTOR gene had a little bit of regeneration but this was not considerable. However, for the final group, it was different. "The group that got visual stimulation plus gene therapy had a significant amount of regeneration, more than had been observed before," he said, adding that the number of retinal ganglion cells that regenerated was a small percentage of the total number. Still, this was much more than had been demonstrated experimentally before, Dr. Huberman said. Making proper connections The cells that did regenerate ulti- mately wired up and performed prop- erly. "We were excited because the connections between the eye and the brain not only regenerated, but they regenerated all the way back into the brain and they connected with the proper areas of the brain," Dr. Huberman said. "We think this has important implications all around Reviving sight with visual stimulation I magine if physicians could re- generate visual nerves that have been damaged due to a disease such as glaucoma. Such is the promise of a new study pub- lished in Nature Neuroscience. Here, investigators showed that with the aid of high-contrast visual stimula- tion they were able to regrow retinal ganglion cells in eyes of mice, according to Andrew Huberman, PhD, professor of neurobiology and ophthalmology, Stanford University School of Medicine, California. One of the issues with nerve cells has been the idea that once they are damaged in adults, it is permanent. "Retinal neurons are like any other neurons in the central nervous system in humans in that they don't regenerate," Dr. Huber- man said. He added that investi- gators wanted to determine if they could regenerate retinal neurons because vision is the sense that humans use the most to navigate the world. In addition, these could serve as a great model for repairing other nerves. "If we could figure out how to regenerate those central nervous system neurons, maybe we could figure out how to regenerate other central nervous system neurons as well," Dr. Huberman said. Four different approaches Investigators started by pinching the optic nerve of mice with forceps. "When you do that, the connections between the eye and the brain rap- idly degenerate. That degeneration is not unlike the degeneration that occurs in common blinding diseases like glaucoma," Dr. Huberman said. After injuring the nerve, inves- tigators then followed one of four different courses. In one group they did nothing. In another, the mice viewed very high-contrast movies several hours a day; Dr. Huberman described these as "kind of like an IMAX theater for mice." In the third group, the mice were given a growth-promoting gene known as mTOR, targeted at neurons. The last Focus on nerve regeneration

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