2011 Progress Report – Executive Summary
Progress on Translational Path
Our primary TPath is in restoration of vision. The efforts, which focused initially on genetic mouse models of retinitis pigmentosa (RP) have expanded to genetic models of RP in dogs and to irradiation-induced models in primate.
- Mouse model. We have made significant progress with both the 2 component (photoswitch + targeted gene) and 1 component (photoswitch only) approaches to reanimating the blind retina following photoreceptor degeneration showing that light-activated glutamate receptors in surviving retinal neurons of mutant mouse models of RP can restore retinal, cortical, and behavioral responses to light.
- Canine model. We added genetically blind canine RP models to the effort as large animal models that more closely represent human vision. Two aspects have been developed: viral gene delivery to RGCs and behavioral assessment in dog models of retinal degeneration.
- Primate model. As an even better model of the human visual system, we have developed a macaque model of visual loss: 647 nm laser induced outer retinal degeneration that kills off photoreceptors and spares retinal ganglion cells. We developed AAVs that deliver genes to these RGCs via intravitreal injection—just as used in mouse. And we developed optical recording using genetically encoded sensors in awake-behaving animals as a complement psychophysical assessment of vision.
Progress in the past year
Progress in the past year included 17 publications (including 2 in Science, 1 in Nature Neuroscience, 1 in Nature Communications, 1 in PLoS Biology, and 2 in Molecular Therapy), as well as 2 submitted papers and 2 patents and several studies that are near completion. Several of these papers represent new collaborations within the NDC. Important among these were:
- The demonstration of an optical pacemaker;
- The demonstration that both the 1 and 2 component systems can restore a simple visually guided behavior in a mouse model of RP;
- The first red-shifted probes;
- The first light-gated GPCR, which hold the promise of enhanced sensitivity to light due to natural amplification.
Dissemination of information about our program was amplified through 25 presentations in major venues.
Up to Top