Next Generation: Photoswitch Chemical Restores Sight

In blind mice, a light-stimulated small molecule temporarily confers photosensitivity to retinal ganglion cells despite rod and cone damage.

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Flat-mounted rat retina at 50x magnificationWIKIMEDIA, MEMORY LAPSEThe compound: Richard Kramer from the University of California, Berkeley, and his colleagues have restored sight to blind mice using a small molecule called DENAQ, which, as a photoswitch chemical, changes conformation in response to light. In healthy mice, vision is a result of the conversion of light energy to electrical energy by specialized photoreceptor cells in the eye. These cells—rods and cones—perceive light and transmit visual information to the retinal ganglion cells (RGCs), which in turn communicate with the brain. Millions of people suffer from progressive degeneration of the rods and cones, which can lead to blindness, such as with diseases like retinitis pigmentosa. However, even after the rods and cones die, RGCs typically remain functional, so researchers have been searching for ways to manipulate them into photosensitivity.

Kramer’s team previously showed that DENAQ could confer light sensitivity on certain voltage gated ion channels. In a paper published today (February 19) in Neuron, the researchers tested its action on three-month-old to six-month-old healthy mice, and on mice carrying a mutation causing nearly all their rods and cones to degenerate by the time they were a month old, by exposing the animals’ retinas to light and recording neuronal activity from the RGCs using an electrode array. They found that RGCs from the diseased-retina mice showed strong light sensitivity after DENAQ treatment.

Retinas with damaged rods and cones are subject to several morphological and biochemical changes, making them different from a healthy retina in more than one way. In this case, Kramer explained, their electrophysiology ...

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