An algae-derived protein that can restore some measure of light sensitivity to mice made blind by retinal degeneration offers a promising first step toward a gene therapy strategy for treating certain types of blindness.

Retinal degeneration disorders, such as the heritable condition retinitis pigmentosa (RP), are leading causes of human blindness. An estimated 1 in 4,000 people worldwide have a genetic predisposition for RP, in which genetic mutations result in loss of photoreceptor neurons in the retina. A suggested potential treatment is the transplantation of healthy cells, but this could entail complex procedures and the risk of host transplant rejection.

In new work published in Neuron (6 April), Wayne State University (Detroit, MI) researcher Zhuo-Hua Pan and his colleagues test another possibility—using gene therapy to introduce a foreign light-sensitive channel protein into the surviving, nonphotosensing neurons of the retina. These neurons normally help transmit the signals generated by photosensors to the brain, but when coaxed into producing the algae-derived light-sensitive ion channel channelrhodopsin-2 (ChR2), seem to acquire limited photosensing capabilities.

Pan's team worked with a mouse model for RP, injecting their eyes with an adeno-associated virus construct that allows infected cells to produce ChR2. They found that RP mice, despite the lack of photosensing neurons, seemed to retain other types of retinal neurons, and that these were readily infected with virus. Neurons producing ChR2 showed substantial light sensitivity, generating action potentials in response to light from a reasonably broad range of visible wavelengths. Importantly, they also demonstrated that the treated RP mice generated visually evoked potentials (i.e., activity in the visual cortex of the brain) in response to light exposure.

This is only a beginning, of course. Among other issues, the light sensitivity is considerably weaker than that in wild-type retinas. Additionally, the cells expressing ChR2 currently show sensitivity only to increasing light intensity; this differs from healthy eyes, in which light sensation results from a balance between neuron classes that sense either increases or decreases in light levels. Pan hopes to address this difference in sensitivity in the near future, perhaps by targeting their virus to specific cell types. In the meantime he indicates that his team is now looking into assessing the impact of this treatment on the visual behavior of rodents—and, in the long term, larger mammalian animal models—to better understand the extent to which once-blind animals benefit from a little additional illumination.