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New Compound May be the Basis of a Promising Drug to Reverse Retinal Blindness

Feb 20, 2014 - Retinal diseases, such as retinitis pigmentosa and age-related macular degeneration (AMD), occur because the eye’s light-sensing photoreceptors are destroyed over time. In the late stages of these conditions, this causes loss of vision. Recent research suggests that a newly-developed “photo-switch” compound may allow other cells in the eye to act as photoreceptors – potentially restoring vision.

The retina has three layers of nerve cells, but only the outer layer contains photoreceptors that respond to light, enabling us to see the world. A “photo-switch” gives light sensitivity to the inner layer of nerve cells (called ganglion cells), even when photoreceptors have none. Detecting light is necessary to transmit information needed for vision.

Dr. Richard Kramer of the University of California, Berkeley and his colleagues have invented "photoswitch" chemicals, which restore light perception to the ganglion cells of blind mice. An earlier version of these chemicals required very bright ultraviolet light, making it unsuitable for medical use. However, a new chemical, named DENAQ, responds to ordinary daylight. Just one injection of DENAQ into the eye of a mouse appeared to give light-sensitivity for several days, and it had no toxic effects.

The new compound has another intriguing quality. In mouse studies using DENAQ, the compound had no effect on nerve cells connected to a functioning photoreceptor. DENAQ allows any undamaged part of the retina to continue functioning normally, while treating only the damaged part. This means that it could be a useful treatment from early stage vision loss to total blindness.

"Further testing…is needed to assess the short- and long-term safety of DENAQ and related chemicals," says Dr. 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."

This research was published in the February 19 issue of the journal Neuron.

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