A New Experimental Chemical Helps Blind Mice See

Photograph of a retina with wet age-related macular degeneration

A new study, published in the July 26, 2012 issue of the journal Neuron, indicates that an injection of the chemical AAQ into the eyes of blind mice can restore light perception temporarily. It also suggests a potential new therapy for persons with blinding retinal diseases, such as age-related macular degeneration and retinitis pigmentosa.

In both of these currently incurable degenerative eye diseases, the light-sensitive cells in the retina, called photoreceptors, no longer function. It is the photoreceptor cells that convert incoming light into electrical impulses and enable us to see.

The Study Authors

The study, entitled Photochemical Restoration of Visual Responses in Blind Mice, was authored by Aleksandra Polosukhina, Jeffrey Litt, Ivan Tochitsky, Joseph Nemargut, Yivgeny Sychev, Ivan De Kouchkovsky, Tracy Huang, Katharine Borges, Dirk Trauner, Russell N. Van Gelder, and Richard H. Kramer, who represent the following institutions: the University of California, Berkeley; the University of Washington; and the University of Munich, Germany.

About the Research

The research team used mice with genetic mutations that caused their retinal photoreceptor cells to become inoperative shortly after birth. The chemical, called AAQ (acrylamide-azobenzene-quaternary ammonium), acts as a type of “photoswitch” that makes the inactive retinal photoreceptor cells “switch on” and become sensitive to light.

The researchers injected small amounts of AAQ into the eyes of the blind mice and were able to confirm that the mouse brains were receiving light signals post-injection: the mouse pupils contracted in bright light and the mice demonstrated light avoidance, which is a behavior typical of sighted mice. You can view a video of the mouse response to light at the UC Berkeley News Center.

According to the authors,

Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are degenerative blinding diseases caused by the death of rods and cones, leaving the remainder of the visual system intact but largely unable to respond to light. Here, we show that AAQ, a synthetic small molecule photoswitch, can restore light sensitivity to the retina and behavioral responses in [live] mouse models of RP…

Intraocular [i.e., within the eye] injection of AAQ restores … light reflex and … light avoidance behavior in mice lacking retinal photoreceptors, indicating reconstitution of light signaling to brain circuits. AAQ and related photoswitch molecules present a potential drug strategy for restoring retinal function in degenerative blinding diseases.

The Future

Newer versions of AAQ are more effective and can activate neurons for days rather than hours; in addition, the research team is planning to conduct more sophisticated vision tests in mice injected with the “next generation” of AAQ.

From a UC Berkeley News Center interview with study authors Richard H. Kramer and Russell N. Van Gelder:

“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.”

“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 can offer them to patients. You can’t do that when you surgically implant a chip or after you genetically modify somebody,” Kramer said.

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 electronic chips in the eye.

VisionAware will provide updates of this innovative and important research as they become available.

Additional sources: Popular Science; Science Daily; ABCNews.com; US News & World Report Health