Blind mice can see again and so might some humans soon. Research published recently by Stanford University School of Medicine shows that visual stimulation can potentially help rewire visual system and in turn partially restore sight in mice.
Funded by a National Institutes of Health (NIH) grant from National Eye Institute and the Glaucoma Research Foundation, the researchers on the project found that high contrast visual stimulation along with increased activity of protein, known as mTOR, promotes regrowth of retinal neurons in the optic nerve of the mice.
The discovery is significant. The Director for National Eye Institute, Paul A Sieving, MD, PHD, explains that reconnecting the broken visual system is actually one of the key challenges when it comes to the development of therapies for eye diseases like glaucoma, which causes blindness.
This new finding shows “that mammals have a greater capacity for central nervous system regeneration than previously known,” says the director in the official NIH press release.
Optic diseases like glaucoma causes loss of eye function due to destruction of cells in optic nerve of the eyes. The optic nerve carries visual information from the eye to the brain where it is processed and an image is registered by the viewer. The optic nerve consists of millions of neurons that have axons, which extend from individual retinal ganglion cells. When these cells are damaged, they do not regenerate on their own.
In the experiment, scientists damaged the optic nerve of the mice with the help of forceps. The damage was only done to one eye of each mouse. All of the mice were then placed in a chamber for several hours over a period of three weeks. In the chamber they were shown high contrast images. The mice showed modest but significant axonal neuron regrowth in the optic nerve.
Combining Two Approaches To Cure Blindness
Previously, the researchers had discovered that increased activity of a protein named mTOR prompted optic nerve generation. To see if there is a synergic effect between two interventions, the scientists decided to combine them both. After three weeks of receiving both therapies, the mice saw more extensive regeneration in the optic nerve.
Encouraged, the scientists decided to shut the good eye of the mice during the exposure to high contrast images, in a new cycle with both interventions. Forcing the mice to see through injured eyes was important to stimulate growth in that particular optic nerve. This helped, by making the mice not rely on the good eye to see. The results were even better this time; neuron regeneration was seen along the full length of optic nerve and also in various visual centers of the brain. In these three weeks the neurons grew nearly 12 millimeters which is 500 times quicker than untreated CNS axons.
Andrew Huberman, PhD, associate professor neurobiology from Stanford University and part of the optic nerve crush model research team, envisions virtual reality video games, television programs, or eyeglasses designed to deliver regeneration-inducing visual stimulation in the future.
Another astonishing finding was that the regrowth seen in the brain visual centers was actually correct and not in portions where it was not needed. Using mouse lines with fluorescent proteins, the researchers tracked where the regenerated axons went. The new retinal ganglion cells, α-cells and melanopsin cells went to correct locations in the brain. The fact that regenerated CNS axons are capable of navigating through correct pathways is pivotal when it comes to regenerative medicine, according to the team.
Visual restoration was judged on the basis of four different indicators: papillary reflex, ability to track a moving object, depth perception, and ability to detect an overhead predator. The mice showed improvement in two out of these four indicators compared to untreated mice. The researchers are also working on a future mouse glaucoma model, as the current model does not mimic typical eye degenerative diseases.
Results of these experiments were published in Nature Neuroscience on July 11, 2016.
Thomas Greenwell, the program director for retinal neuroscience research at National Eye Institute, said that the “finding that activity promotes nerve regrowth holds great promise for therapies aimed at degenerative retinal diseases” and will help with overall efforts of the institute to develop regenerative medicine for retinal diseases.
The most common degenerative retinal diseases are age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Patients with RP are considered legally blind by the age 40. WHO estimates that 5% of total blindness cases worldwide are due to AMD.
Currently, 170 and 1.5 million people worldwide are living with AMD and retinitis pigmentosa, respectively. According to estimates, in the year 2020, the number of people suffering from AMD would be 196 million and in the year 2040 the number will be 288 million. In United States, AMD affects 15 million people, and RP affects nearly 100, 000 people.