Newly developed chemical restores light perception in blind mice
February 27, 2014
Richard Kramer of the University of California, Berkeley and his colleagues have invented a “photoswitch” chemical named DENAQ that confers light sensitivity on normally light-insensitive retinal ganglion cells, restoring light perception in blind mice.*
An earlier photoswitch investigated by the researchers in 2012 (reported by KurzweilAI) called AAQ requires very bright ultraviolet light, which can be damaging; and AAQ dissipates from the eye within a day after injection.
But just one injection of DENAQ into the eye confers light sensitivity for several days with ordinary white light.
As described in a study appearing in the February 19 issue of the Cell Press journal Neuron, the compound may be a potential drug candidate for treating patients suffering from degenerative retinal disorders.
Experiments on mice with functional, nonfunctional, or degenerated rods and cones showed that DENAQ only impacts retinal ganglion cells if the rods and cones have already died. It appears that degeneration in the outer retina leads to changes in the electrophysiology in the inner retina that enables DENAQ photosensitization, while the presence of intact photoreceptors prevents DENAQ action.
“Further testing on larger mammals is needed to assess the short- and long-term safety of DENAQ and related chemicals,” says 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.”
* Progressive degeneration of photoreceptors — the rods and cones of the eyes — causes blinding diseases such as retinitis pigmentosa and age-related macular degeneration. The retina has three layers of nerve cells, but only the outer layer contains the rod and cone cells that respond to light, enabling us to see the world. When the rods and cones die during the course of degenerative blinding diseases, the rest of the retina remains intact but unable to respond to light. Even though the innermost layer’s nerve cells, called retinal ganglion cells, remain connected to the brain, they no longer transmit information useful for vision.
Abstract of Neuron paper
- DENAQ photosensitizes blind retinas to white light with intensity similar to daylight
- Photosensitization in vivo lasts for days after a single intraocular injection
- DENAQ photosensitizes retinal ganglion cells only if the rods and cones have degenerated
- DENAQ restores light-elicited behavior and enables visual learning in blind mice
Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are blinding diseases caused by the degeneration of rods and cones, leaving the remainder of the visual system unable to respond to light. Here, we report a chemical photoswitch named DENAQ that restores retinal responses to white light of intensity similar to ordinary daylight. A single intraocular injection of DENAQ photosensitizes the blind retina for days, restoring electrophysiological and behavioral responses with no toxicity. Experiments on mouse strains with functional, nonfunctional, or degenerated rods and cones show that DENAQ is effective only in retinas with degenerated photoreceptors. DENAQ confers light sensitivity on a hyperpolarization-activated inward current that is enhanced in degenerated retina, enabling optical control of retinal ganglion cell firing. The acceptable light sensitivity, favorable spectral sensitivity, and selective targeting to diseased tissue make DENAQ a prime drug candidate for vision restoration in patients with end-stage RP and AMD.