The nursery rhyme “Three Blind Mice” now describes a thing of the past, considering recent developments in the recovery of eyesight in blind mice. Previously, no cure existed for blindness, which was thought to be a permanent condition. The research conducted by the Stanford University School of Medicine, however, proves otherwise.
A team led by Andrew Huberman, an associate professor of neurobiology who heads a neural vision lab at Stanford, explored the growth of optic nerves of mice to find potential methods of reversing potential damage. Vision is only possible when light bounces off an object and enters the eye. There, the lens focuses the light onto the retina, where photoreceptor cells detect and transmit the information to retinal ganglion cells; once the axons of those cells are damaged, they cannot regenerate as the mTOR pathway, a growth-enhancing sequence of molecular interactions, tails off over time. Since retinal ganglion cells are the only ones that link the eye to the brain, any damage to them results in blindness.
Huberman and his team crushed the nerve in one eye of the mice, but kept the photoreceptor cells and their connections to the retinal ganglion cells intact. They observed that the axons that connect the eye to the brain immediately began to shrivel, disrupting the interconnecting signals and causing blindness.
The researchers soon found that the use of nerve-growing chemicals and visual stimulation could alter this outcome. They exposed one group of mice to biochemical manipulations that increased the activity of mTOR pathway within the retinal ganglion cells, another group to high-contrast images of a moving black and white grid, both of which exercised the axons and prevented their atrophy, and the rest to both forms of treatment. The researchers found that only the mice that received both procedures saw drastic improvement in their vision. When the procedures were completed before the optic nerve was completely lost, the procedures salvaged the axons, allowing them to regenerate despite having been completely severed. Besides producing a 500-fold increase in axon regrowth, this study also shows that axons seem to permanently retain instructions for appropriate connections to the brain; in other words, “...Neurons remember the way home; they never forget,” said Huberman.
But how much of this regrowth actually translates to a restoration of sight? After three weeks of the treatment, the researchers conducted four different tests to see the potential for long-term improvement of vision in the mice. Most of the mice passed one test concerning larger objects and movement, which involved the projection of an expanding dark circle that mimicked the approach of a predator. The majority of the mice noticed and headed towards safety, confirming that most of the axons had reattached to their proper respective locations in the brain. These findings also indicated that the mice had at least partially recovered from their blindness because they were able to respond to the projection.
However, the mice were unable to discern finer details in the the other tests. Thus, the researchers were able to confirm that axons from two specific retinal ganglion cell types successfully reached their targets, but not those of other relevant cell types, of which there are 30 or so. To make further progress, a better understanding of the variety and the complexity of those cells is needed in order to determine how to best help a greater number of the axons successfully recover and reestablish connections with their respective structures of the brain.
These findings have many implications for the remedying of blindness in humans. Glaucoma, pituitary tumors, brain cancers, and general injuries can all cause optic nerve damage and subsequently, blindness. With this new research, doctors could potentially revert damage to the optic nerve, as long as they detect it before the nerves completely deteriorate.
Huberman and his team will continue to work on the project and is hopeful that something will come into fruition within five years.
References:
1. Park, Alice. (2016, July 11). In a scientific first, blind mice regain eyesight. Retrieved April 14, 2017, from http://time.com/4399255/mice-blindness-cure/
2. Goldman, Bruce. (2016, July 11). First-ever restoration of vision achieved in mice. Retrieved April 14, 2017, from https://med.stanford.edu/news/all-news/2016/07/first-ever-restoration-of-vision-achieved-in-mice.html
3. Paddock, Catharine. (2016, July 12). Scientists restore key parts of vision in blind mice for first time. Retrieved April 14, 2017, from http://www.medicalnewstoday.com/articles/311600.php