Science

Chemical found to temporarily restore sight in blind mice

Chemical found to temporarily restore sight in blind mice
Researchers have discovered that the chemical AAQ temporarily restores some sight in blind mice and hope it could one day be used in humans (Image: Shutterstock)
Researchers have discovered that the chemical AAQ temporarily restores some sight in blind mice and hope it could one day be used in humans (Image: Shutterstock)
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Researchers have discovered that the chemical AAQ temporarily restores some sight in blind mice and hope it could one day be used in humans (Image: Shutterstock)
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Researchers have discovered that the chemical AAQ temporarily restores some sight in blind mice and hope it could one day be used in humans (Image: Shutterstock)

Researchers have discovered a chemical that makes cells in the retinas of blind mice sensitive to light, temporarily restoring some vision. They are working on an improved compound that they hope could one day be used to restore sight in human patients suffering from retinitis pigmentosa, the most common form of inherited blindness, and macular degeneration, the most common cause of acquired blindness in the developed world.

The vision-restoring chemical under examination by researchers from the University of California, Berkeley, the University of Munich and University of Washington in Seattle, is known as AAQ ((acrylamide-azobenzene-quaternary ammonium). It is a photoswitch that binds to protein ion channels on the surface of retinal cells which, when turned on, alters the flow of ions through the channels and activates neurons in a similar way to which the rod and cone photoreceptors in the retina 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,” said lead researcher Richard Kramer, UC Berkeley professor of molecular and cell biology. “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.”

Unlike gene or stem cell therapies, which permanently change the retina, the effect is temporary as the chemical eventually wears off. While this may appear to be a negative, the researchers say the chemical may offer a safer alternative to other experimental approaches for restoring sight. It is also less invasive than implanting light-sensitive electronic chips into 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.

The blind mice in the team’s study had genetic mutations that caused their rods and cones to die within months of birth and inactivated other photopigments in the eye. After very small amounts of AAQ were injected into the eyes of the mice, their pupils contracted in bright light and they exhibited light avoidance, indicating light sensitivity had been restored. The team hopes to conduct more sophisticated vision tests in rodents injected with the next generation of the compound.

Kramer says new versions of AAQ that are currently being tested are much improved, activating neurons for days rather than hours. The previous compound used ultraviolet light to activate the neurons and green light to deactivate them. However, the new versions are activated using blue-green light of moderate intensity and naturally deactivate in darkness instead of needing a second color light to turn them off.

“The photoswitch approach offers real hope to patients with retinal degeneration,” said co-author Dr. Russell Van Gelder, an ophthalmologist and chair of the Department of Ophthalmology at the University of Washington, Seattle. “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.”

Tests of the original AAQ compound are detailed in the journal Neuron.

Source: UC Berkeley

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