Degenerative diseases of the outer retina lead to photoreceptor loss and eventually cause blindness. However, retinal ganglion cells (RGCs) are relatively preserved. Artificial photo-stimulation of these functional cells, using optogenetic probes like Channelrhodopsin-II, could be the key to developing minimally invasive, high resolution retinal neuroprosthetic devices, which will restore patients' vision. A successful retinal prosthesis should induce activity patterns enabling downstream circuits to correctly interpret the artificially generated stimulus as the intended image. Previous work done in our lab demonstrated single-cell resolved optogenetic photo-stimulation of RGCs in vitro.

The research presented here constitutes a first step in advancing towards in vivo retinal stimulation. First, we describe the choice of model animals and the derivation of cross-bred transgenic mice that co-express genes for outer retinal degeneration and for Channelrhodopsin-II. Next, we present a system which integrates precise spatiotemporal holographic photo-stimulation of retinal cells with high resolution fundus imaging, capable of targeting patterns at specific locations with near single-cell resolution, in order to excite RGCs in mouse retinas in-vivo. Finally, we describe preliminary work towards functional calcium imaging of neuronal population activity, in the retina and the brain.

This work forms an important step towards the development of a novel optical retinal prosthesis.