Researchers regenerate optic nerve in mice

Individuals blinded by optic nerve damage from glaucoma or trauma might be able to regain at least some visual function in the future after researchers have successfully regenerated the optic nerve in mice. Using a combination of three methods, Larry Benowitz, Ph.D., and his team at the F.M. Kirby Neurobiology Center at Boston Children's Hospital, were able to restore some depth perception in mice with severe optic nerve damage. In addition, they found that the mice regained the ability to detect overall movement of the visual field, and perceive light. The study is published online by the Proceedings of the National Academy of Sciences. Although earlier studies have shown that optic nerve fibers can regenerate some distance through the optic nerve, this study is the first to demonstrate that these fibers can be made to grow long enough to go from eye to brain. The researchers found that the fibers are able to find their way to the correct visual centers in the brain, are wrapped in the conducting insulation known as myelin, and can make connections (synapses) with other neurons, allowing visual circuits to re-form. Nareej Agarwal, Ph.D., of the National Eye Institute, explained: "Dr. Benowitz and his group have, for the first time, established proof-of-concept that a damaged optic nerve can regenerate and attain lost function. This is an important advance in an effort to reverse vision loss in glaucoma and other neurodegenerative diseases." The researchers combined three methods of activating the growth state of neurons in the retina and found they had a synergistic effect on growth of optic nerve fibers. Benowitz, who is also a director of the Laboratories for Neuroscience Research in Neurosurgery at Boston Children's Hospital, said: "Sixteen years ago, people said it was impossible to get any regeneration in the optic nerve. Our study regenerated only a small percentage of the total number of fibers that would normally come into the brain, but it answers questions that have been real unknowns in the field." Although some basic elements of vision were restored in the mice, the ability to discriminate objects was probably not, said Benowitz. He continues: "What lies behind what we call seeing is very complicated - so many subsystems contribute to seeing. We're in a sense just scratching the surface about functional recovery." The researchers found that: Treated mice were able synchronize their sleep/wake cycles. In a depth perception test, mice with regeneration were less likely to walk off the edge of a plexiglass platform above a checkerboard pattern than untreated mice. When treated mice were put on a platform surrounded by rotating vertical stripes, they moved their heads reflexively to follow the pattern. According to Benowitz, the molecular manipulations the team conducted in the mice would need to be altered in order to develop an actual treatment for patients. Benowitz said: "The eye turns out to be a feasible place to do gene therapy. The viruses used to introduce various genes into nerve cells mostly remain in the eye. Retinal ganglion cells are easily targetable."