Despite the current enthusiasm for optogenetic vision restoration, there is remarkably little direct evidence about whether it can reverse blindness in humans. The feasibility of optogenetics was first suggested by studies from many labs that showed restoration of neuronal visual responses and visually guided behaviors in previously blind mice or dogs. These studies have been very informative in exploring interventions to treat retinal diseases genetically identical to some human disorders. However, they have not addressed restoration in an animal model that closely matches human vision, nor have they examined the perceptual quality of the restored vision. In the studies proposed here, we will address these two issues, first by using macaque monkeys in all studies, the animal model that most resembles humans in visual structure and function, and second by examining the range of visual perceptual abilities made possible by optogenetics. We will use a recently developed in-vivo physiology method to study vision restoration at the level of individual retinal cells in macaque monkeys. This approach will be used in the first aim to examine at a cellular level the spatial, temporal and sensitivity responses of macaque retinal neurons produced by optogenetic restoration. In the second aim we will use controlled fixation psychophysical testing of macaques to examine the range of visual capabilities provided by channelrhodopsin restoration, something that has never been studied. Finally, we will examine the duration of optogenetic restoration, measuring any long-term decrease in function or practice-related improvement in visual function.
The goal of this research is examine optogenetically restored vision in non- human primates to guide future restoration of vision in blind humans. We will use in-vivo adaptive optics imaging and controlled fixation psychophysical methods in macaque to examine visual responses provided by ganglion cell and ON bipolar cell optogenetics, something that has never been accomplished. We will also use psychophysical methods to study the duration of optogenetic restoration in macaques, examining the possibility of either degraded restoration or improved visual performance as the monkeys learn to use the restored visual signals.
| Cheong, Soon Keen; Strazzeri, Jennifer M; Williams, David R et al. (2018) All-optical recording and stimulation of retinal neurons in vivo in retinal degeneration mice. PLoS One 13:e0194947 |
| Cheong, Soon K; Xiong, Wenjun; Strazzeri, Jennifer M et al. (2018) In Vivo Functional Imaging of Retinal Neurons Using Red and Green Fluorescent Calcium Indicators. Adv Exp Med Biol 1074:135-144 |
| Marcos, Susana; Werner, John S; Burns, Stephen A et al. (2017) Vision science and adaptive optics, the state of the field. Vision Res 132:3-33 |
| Kotterman, M A; Yin, L; Strazzeri, J M et al. (2015) Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates. Gene Ther 22:116-26 |
| Yang, Qiang; Yin, Lu; Nozato, Koji et al. (2015) Calibration-free sinusoidal rectification and uniform retinal irradiance in scanning light ophthalmoscopy. Opt Lett 40:85-8 |
| Strazzeri, Jennifer M; Hunter, Jennifer J; Masella, Benjamin D et al. (2014) Focal damage to macaque photoreceptors produces persistent visual loss. Exp Eye Res 119:88-96 |
| Sharma, Robin; Yin, Lu; Geng, Ying et al. (2013) In vivo two-photon imaging of the mouse retina. Biomed Opt Express 4:1285-93 |
| Yin, Lu; Geng, Ying; Osakada, Fumitaka et al. (2013) Imaging light responses of retinal ganglion cells in the living mouse eye. J Neurophysiol 109:2415-21 |
| Geng, Ying; Dubra, Alfredo; Yin, Lu et al. (2012) Adaptive optics retinal imaging in the living mouse eye. Biomed Opt Express 3:715-34 |
