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Chemical Treatment Restores Partial Vision to Blind Mice

An estimated 3.4 million people suffer from retinal pigmentosa (RP) or age-related macular degeneration (AMD) in the United States alone. These diseases deteriorate retinal function and result in various degrees of vision loss, including complete blindness. Current treatment methods can slow the onset of these diseases, but there is nothing that can be done to reverse the loss of vision once it occurs. This might not always be the case, as a new chemical called DENAQ has been shown to restore photosensitivity of retinal cells. The study was led by Richard Kramer from University of California Berkeley and the results were published in Neuron. The retina is located at the posterior end of the eyeball. Light comes in through the lens and is focused on the retinal cells. Rods are sensitive photoreceptors which are better adapted to low-light scenarios while cones are the color-sensitive cells. The data they collect is transmitted through the ganglion cells, which sends the information to various regions of the brain but are not sensitive to light themselves. Due to age and/or genetic factors, the rods and cones can begin to lose function, decreasing the quality and quantity of visual information sent to the brain via the ganglion cells. Physically, all the retinal cells are still there, but have ceased to function properly.

A molecule known as AAQ was developed several years ago by Kramer’s lab and could act as a “photoswitch” to make the ganglion cells photosensitive and restore partial vision. Unfortunately, high levels of ultraviolet light were required to make them function and the dose only lasted a few hours. These limitations made it completely unsafe and impractical for use in a living organism. Kramer et al. later developed a molecule that was shown to make the ganglion cells photosensitive and required only the use of regular daylight – a marked improvement over AAQ. The new chemical was named DENAQ. The most recent study applied DENAQ into blind mice for in vivo testing. The mice had a genetic condition that rapidly degenerated rod and cone function within the first month of life, but were otherwise healthy. Not only does the disease decrease vision, but also alters the electrophysiology. Mice who received DENAQ (along with a control group) were monitored in both normal and low-light conditions as the researchers watched their movements. The test group was able to navigate their surroundings and showed signs of visual learning much better than the control group after receiving the treatment. The addition of a small electric shock also helped the mice re-learn how to process light. DENAQ is injected into the eye and the results can last for several days. The chemical is able to target only the ganglion cells that do not accompany functional rods and cones. According to Kramer, this should minimize any side effects. However, even after a month of study, there was no indication that DENAQ had any toxic effects on the test subjects.  Of course, this is a long way off from human trials, let alone clinical application. It is still not entirely understood how DENAQ impacts vision or if it could affect other processes in the brain due to the change in ganglion cell function. Also, while mice are a great first model organism, there is still the possibility that DENAQ could be toxic in humans. Future research will try DENAQ in other mammals to determine if it shows the same success as in the mice.

The capacity of the brain to rewire itself has given hope to stroke victims and people who have survived injuries, but now is being turned to something with even more widespread appeal – helping baseball players hit the ball more often. Ultimeyes is an app whose makers claim 30 minutes use a day will train the brain to pick up images at distance with less blurring. While its existence might have been a disaster for the impressionist art movement, its promise is tantalizing for sports players who need to sight a fast moving ball as early and accurately as possible.  The visual cortex of the brain turns signals from the eyes to fuzzy patterns. UltimEyes presents us with these patterns directly in the hope the brain will learn to process them more efficiently. Users have to identify faint and fuzzy patterns, which get fainter and fuzzier the better the user gets. The makers describe it as operating as a game to “heighten levels of engagement and the provide positive reinforcement required to drive progress.” Cues, distractions and task length are adapted to match an individual player’s progress.
While this might all sound like a new marketing angle for just another video game, peer reviewed research backs Ultimeyes up. Current Biology reports that when members of the University of California Riverside (UCR) Baseball Team used the test their performance on standard eye-charts improved, and so did their batting. Inventor Associate Professor Aaron Seitz of the UCR Department of Psychology claims the training accounted for an extra 4-5 wins in the first season. However, the fact that allocation to the test group wasn’t random and that team members who were not included in the study had no placebo may have exaggerated the gap between the players who participated and those that did not. On Reddit, Seitz said,  If focus is not ideal, there is a stigmatism, a scotoma, etc, then the brain can learn to do the best with what it is given but the problem with the input will remain. This said, it is important to realize that there are two general causes of poor vision, those related to ocular impairments for which improvement of the eye-function is required, and brain-based impairments for which brain training can help. Typically we suffer from a mixture of these and thus brain training can give some advantage even without ocular improvement and vise-versa.  The app is being tested on people with low-vision, but results are yet to be confirmed. “Research is slow when months of training is required,” said Seitz. The study reported remarkable results for some players. Average distance at which players could see clearly improved by 31% and seven members of the team achieved 20/7.5 vision – equivalent to seeing a chart 20 feet away as clearly as someone with normal vision could see at 7.5 feet – despite starting from roughly normal. Confirmation of such potential might help explain the puzzle as to why Indigenous Australians have better eyesight than other racial groups, even when refractive errors are controlled for and lends credibility to stories of freakish eyesight, such as the capacity of some individuals to find stars several magnitudes below normal vision or see land from 30 miles out to sea.
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