NEUROLOGY/OPHTHALMOLOGY: Light-activatable engineered molecule promising for AMD, epilepsy treatment

Collaboration between chemists and vision scientists has resulted in the design of a light-sensitive molecule able to trigger response in cells of the retina and brain.1 The achievement is seen as a possible first step in overcoming degenerative eye diseases such as age-related macular degeneration (AMD; the leading cause of vision loss in people over 50), and to dampening epileptic seizures.

David Pepperberg is principal investigator on a study that bypasses rods and cones to make the retina's
David Pepperberg is principal investigator on a study that bypasses rods and cones to make the retina's "inner cells" responsive to light. The approach may also work as a treatment for epilepsy. (Image courtesy of UIC Photo Services)

AMD results when the retina's rods and cones—which normally absorb light and initiate visual signals—are lost. In such cases, the "inner cells" of the retina may still be operational. "Our approach is to bypass the lost rods and cones, by making the inner cells responsive to light," said David Pepperberg, professor of ophthalmology and visual sciences in the University of Illinois Chicago (UIC) College of Medicine.

Pepperberg, principal investigator on the study, is working with colleagues to develop light-sensitive molecules that—when injected into the eye—attach to inner retinal cells and initiate the signal that is sent to the brain. In collaboration with chemists led by Karol Bruzik in UIC's College of Pharmacy, they have developed a compound that dramatically regulates the GABA receptors of both an engineered receptor system and native receptors of retinal ganglion cells and brain neurons. When struck by light of different wavelengths, the molecule changes shape and functions as a light-triggered, on-off switch for these receptors.

Experiments done in collaboration with neurobiologist Thomas Otis at the University of California at Los Angeles demonstrated that the approach applies beyond visual systems. "Photo-regulation may also have potential as a therapeutic for epilepsy, a class of diseases that involves abnormal excitatory activity in the brain," said Pepperberg.

1. L. Yue, Nat. Comm., 3, 1095, doi:10.1038/ncomms2094.

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