M.Sc Thesis

M.Sc StudentTsur Limor
SubjectSystem for Holographic Stimulation of the Optogenetic Probe
Channelrhodopsin II in Retinal Cells in vivo
DepartmentDepartment of Biomedical Engineering
Supervisor PROF. Shy Shoham
Full Thesis textFull thesis text - English Version


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.