Jean Bennett, MD, PhD and Therese Cronin, PhD
Posted: June 2, 2011
LiGluR Restores Visual Responses in Rodent Models of Inherited Blindness
Natalia Caporale, Kathleen D Kolstad, Trevor Lee, Ivan Tochitsky, Deniz Dalkara, Dirk Trauner, Richard Kramer, Yang Dan, Ehud Y Isacoff and John G Flannery
Gene augmentation therapy holds great promise for treatment of specific inherited forms of retinal degeneration, but success is limited by the extent of disease. Once the photoreceptors have degenerated they can no longer be resuscitated. The study by Caporale and colleagues, many of whom are at the University of California, Berkeley, explores a strategy which could potentially be used long after the photoreceptors have degenerated, as it assigns the task of light detection to the surviving ganglion cells. Caporale et al. delivered an artificial optical switch whose ability to respond to light is controlled by a companion chemical compound, maleimide-azobenzene-glutamate (MAG). The optical switch was delivered to ganglion cells using the same type of recombinant viral vector that is being used safely and successfully in gene augmentation therapy clinical trials.
In the Caporale study, when MAG was present, these cells became responsive to light of the appropriate wavelength. Further, the retinal-cortical circuits which control pupillary light reflexes were restored and the animals developed vision. While vision wasn’t of the quality of a normal-sighted mouse, it was sufficient to provide the animals with light avoidance behavior. This sort of sensation could potentially improve navigational abilities in blind individuals.
Before this approach is tested in humans, the reagents can be fine-tuned to allow the switch to respond to optimal wavelengths of light and to provide a long-lasting supply of the companion inducer, MAG. This generic therapeutic approach, which could potentially be supplied through a single office procedure (intravitreal injection), provides hope for people blinded by a diverse set of inherited and acquired retinal degenerations.