AAQ chemical makes blind mice see; compound holds promise for treating humans

July 25, 2012

A team of University of California, Berkeley, scientists in collaboration with researchers at the University of Munich and University of Washington in Seattle has discovered a chemical that temporarily restores some vision to blind mice, and is working on an improved compound that may someday allow people with degenerative blindness to see again.

The approach could eventually help those with retinitis pigmentosa, a genetic disease that is the most common inherited form of blindness, as well as , the most common cause of acquired in the developed world. In both diseases, the in the — the rods and cones — die, leaving the eye without functional photoreceptors.

The chemical, called AAQ, acts by making the remaining, normally "blind" cells in the retina sensitive to , said lead researcher Richard Kramer, UC Berkeley professor of molecular and cell biology. AAQ is a photoswitch that binds to protein ion channels on the surface of retinal cells. When switched on by light, AAQ alters the flow of ions through the channels and activates these neurons much the way rods and cones are activated by light.

"This is similar to the way local anesthetics work: they embed themselves in ion channels and stick around for a long time, so that you stay numb for a long time," Kramer said. "Our molecule is different in that it's light sensitive, so you can turn it on and off and turn on or off neural activity."

Because the chemical eventually wears off, it may offer a safer alternative to other experimental approaches for restoring sight, such as gene or stem cell therapies, which permanently change the retina. It is also less invasive than implanting light-sensitive chips in the eye.

"The advantage of this approach is that it is a simple chemical, which means that you can change the dosage, you can use it in combination with other therapies, or you can discontinue the therapy if you don't like the results. As improved chemicals become available, you could offer them to patients. You can't do that when you surgically implant a chip or after you genetically modify somebody," Kramer said.

"This is a major advance in the field of vision restoration," said co-author Dr. Russell Van Gelder, an ophthalmologist and chair of the Department of Ophthalmology at the University of Washington, Seattle.

Kramer, Van Gelder, chemist Dirk Trauner and their colleagues at UC Berkeley, the University of Washington, Seattle, and the University of Munich will publish their findings Thursday, July 26, in the journal Neuron.

The blind mice in the experiment had genetic mutations that made their rods and cones die within months of birth and inactivated other photopigments in the eye. After injecting very small amounts of AAQ into the eyes of the blind mice, Kramer and his colleagues confirmed that they had restored light sensitivity because the mice's pupils contracted in bright light, and the mice showed light avoidance, a typical rodent behavior impossible without the animals being able to see some light. Kramer is hoping to conduct more sophisticated vision tests in rodents injected with the next generation of the compound.

"The photoswitch approach offers real hope to patients with retinal degeneration," Van Gelder said. "We still need to show that these compounds are safe and will work in people the way they work in mice, but these results demonstrate that this class of compound restores light sensitivity to retinas blind from genetic disease."

From optogenetics to implanted chips

The current technologies being evaluated for restoring sight to people whose rods and cones have died include injection of stem cells to regenerate the rods and cones; "optogenetics," that is, gene therapy to insert a photoreceptor gene into blind neurons to make them sensitive to light; and installation of electronic prosthetic devices, such as a small light-sensitive retinal chip with electrodes that stimulate blind neurons. Several dozen people already have retinal implants and have had rudimentary, low vision restored, Kramer said.

Eight years ago, Kramer, Trauner, a former UC Berkeley chemist now at the University of Munich, and their colleagues developed an optogenetic technique to chemically alter potassium ion channels in blind neurons so that a photoswitch could latch on. Potassium channels normally open to turn a cell off, but with the attached photoswitch, they were opened when hit by ultraviolet light and closed when hit by green light, thereby activating and deactivating the neurons.

Subsequently, Trauner synthesized AAQ (acrylamide-azobenzene-quaternary ammonium), a photoswitch that attaches to potassium channels without the need to genetically modify the channel. Tests of this compound are reported in the current Neuron paper.

New versions of AAQ now being tested are better, Kramer said. They activate neurons for days rather than hours using blue-green light of moderate intensity, and these photoswitches naturally deactivate in darkness, so that a second color of light is not needed to switch them off.

"This is what we are really excited about," he said.

Explore further: Why the eye is better than a camera at capturing contrast and faint detail simultaneously

Related Stories

Why the eye is better than a camera at capturing contrast and faint detail simultaneously

May 3, 2011
The human eye long ago solved a problem common to both digital and film cameras: how to get good contrast in an image while also capturing faint detail.

Optogenetic technology restores visual behavior in mice, holds promise for treating human blindness

April 20, 2011
There are more than 1 million blind people in the U.S., and about 100,000 of those lost their sight due to retinitis pigmentosa, a disease that destroys light-sensitive cells in the retina.

Scientists unravel the cause of rare genetic disease: Goldman-Favre Syndrome explained

August 31, 2011
A new research report published in The FASEB Journal will help ophthalmologists and scientists better understand a rare genetic disease that causes increased susceptibility to blue light, night blindness, and decreased vision ...

Recommended for you

Team constructs whole-brain map of electrical connections key to forming memories

November 22, 2017
A team of neuroscientists at the University of Pennsylvania has constructed the first whole-brain map of electrical connectivity in the brain based on data from nearly 300 neurosurgical patients with electrodes implanted ...

To forget or to remember? Memory depends on subtle brain signals, scientists find

November 22, 2017
The fragrance of hot pumpkin pie can bring back pleasant memories of holidays past, while the scent of an antiseptic hospital room may cause a shudder. The power of odors to activate memories both pleasing and aversive exists ...

New research suggests high-intensity exercise boosts memory

November 22, 2017
The health advantages of high-intensity exercise are widely known but new research from McMaster University points to another major benefit: better memory.

Pitch imperfect? How the brain decodes pitch may improve cochlear implants

November 22, 2017
Picture yourself with a friend in a crowded restaurant. The din of other diners, the clattering of dishes, the muffled notes of background music, the voice of your friend, not to mention your own – all compete for your ...

What if consciousness is not what drives the human mind?

November 22, 2017
Everyone knows what it feels like to have consciousness: it's that self-evident sense of personal awareness, which gives us a feeling of ownership and control over the thoughts, emotions and experiences that we have every ...

Now you like it, now you don't: Brain stimulation can change how much we enjoy and value music

November 20, 2017
Enjoyment of music is considered a subjective experience; what one person finds gratifying, another may find irritating. Music theorists have long emphasized that although musical taste is relative, our enjoyment of music, ...

3 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

AnyLabTestNow
not rated yet Jul 25, 2012
Can you use the same aproach and make retinal cell sensitive to diferent wavelengths of light? Could you enhance normal vision to be sensitive to UV or IR spectrum?
C_elegans
not rated yet Jul 25, 2012
That's actually a pretty good idea.
C_elegans
not rated yet Jul 25, 2012
"Potassium channels normally open to turn a cell off, but with the attached photoswitch, they were opened when hit by ultraviolet light and closed when hit by green light, thereby activating and deactivating the neurons."

Sounds like that's the first thing they did! I wonder what it's like to be those mice.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.