Chemical that restores light vision in mice could lead to new treatment for blindness

Did you ever see such a sight in your life? Cindy Cornett Seigle/Flickr, CC BY-NC

Scientists have developed a new chemical they claim can restore light sensitivity in blind mice. The compound, called DENAQ, acts as a “photoswitch” that can turn on light-sensitive cells in retinas when injected into the eyes. Each injection enabled blind mice to respond to normal levels of light perception for several days.

The authors of the study, published in Neuron, said the compound could potentially be used to treat human patients suffering from degenerative eye conditions such as age-related macular degeneration and retinitis pigmentosa – diseases caused by progressive degeneration of the receptors in our eyes that process light. Eye diseases such as these affect millions globally and there is currently no cure.

Rods and cones

The retina has three layers of nerve cells, but only the outer layer contains the rod and cone cells that respond to light, enabling us to see the world. During the course of degenerative blindness, these rods and cones die. While the rest of the retina remains intact it is stripped of the functional photoreceptors – the rods and cones – and leaves sufferers unable to respond to light. Even though the nerve cells in the eye’s innermost layer remain connected to the brain, without the photoreceptors they can no longer transmit information useful for vision.

DENAQ makes these nerve cells in the retina respond to light by binding itself to proteins on their surface. When switched on by light, the chemical activates brain cells in much the same way as rods and cones are triggered. Mice with degenerated rods and cones that were injected with the compound became sensitive to light were able to detect light enough to influence behaviour in tasks set by researchers.

Getting regular injections in your eye may sound like an unpleasant experience, but the developers of the jab emphasise that it is a less invasive method that is more flexible than other technologies being developed to restore sight to people whose rods and cones have died. These include surgically injecting stem cells into the eyes to regenerate rods and cones, gene therapy, which uses a virus to insert a photoreceptor gene into “blind” neurons to make them sensitive to light, or installing prosthetic retinal devices.

The new compound is an improvement on earlier research where the same team created a chemical called AAQ. This performed a similar function of restoring light sensitivity in blind mice, but required bright ultraviolet light, making it unsuitable for medical use in humans.

“The new chemical DENAQ is a great improvement over our previous photoswitch AAQ,” Richard Kramer, professor of molecular and cell biology at the University of California, Berkeley, who led the study, said. “It responds to normal daylight-intensity, white light, it is non-toxic, and it persists in the eye for at least a few days.”

Limited vision

It’s clearly still early days for the findings and the ability of the chemical compound to restore vision is still very limited. Robin Ali, professor of human molecular genetics at UCL’s Institute of Ophthalmology, said. “This paper provides good evidence that the new drug can be used to illicit light perception. There is no evidence that application of the drug results in any sort of useful vision yet.”

Also, the study shows that DENAQ “only impacts ganglion cells if the rods and cones have already died” Ali said. In other words, this would only ever be a potential treatment for individuals who had lost all vision and light perception – those with advanced retinitis pigmentosa, but not age-related macular disease in the compound’s present form.

Restoring some vision “might be possible”, he said. “But this needs to be demonstrated and is unlikely to give good vision as there would be a lack of processing of signals within the retina. Perhaps the brain could learn to interpret the new information, but this needs to be demonstrated.”

Testing for toxicity

The compound’s toxicity is one that also needs to be explored further if the chemical is going to be developed for human use. “The toxicity study was very short term. It is also not clear that the drug would be safe if used repeatedly and over a long period,” Ali said.

Dirk Trauner, professor of chemical biology and genetics at the University of Munich and study co-author, said it was something they would be working on. “We are currently doing toxicology studies and are working on more selective compounds with improved pharmacodynamics (the effects of the drug on the body),” he said.

“All drugs have side effects, but this finding implies that DENAQ will have very few,” added Kramer. “It will take several more years, but if safety can be established, these compounds might ultimately be useful for restoring light sensitivity to blind humans. How close they can come to re-establishing normal vision remains to be seen.”