Photogenetic Retinal Prosthesis

Abstract

The last few decades have witnessed an immense effort to develop working retinal implants for patients suffering from retinal degeneration diseases such as retinitis pigmentosa. However, it is becoming apparent that this approach is unable to restore levels of vision that will be sufficient to offer significant improvement in the quality of life of patients. Herein, a new type of retinal prosthesis that is based on genetic expression of microbial light sensitive ion channel, Chanelrhodopsin-2 (ChR2), and a remote light stimulation is examined. First, the dynamics of the ChR2 stimulation is characterized and it is shown that (1) the temporal resolution of ChR2-evoked spiking is limited by a continuous drop in its depolarization efficiency that is due to (a) frequency-independent desensitization process and (b) slow photocurrent shutting, which leads to a frequency-dependent post-spike depolarization and (2) the ChR2 response to light can be accurately reproduced by a four-state model consisting of two interconnected branches of open and close states. Then, a stimulation prototype is developed and its functionality is demonstrated in-vitro. The prototype uses a new micro-emissive matrix which enables generating of two-dimensional stimulation patterns with enhanced resolution compared to the conventional retinal implants. Finally, based on the micro-emitters matrix, a new technique for sub-cellular and network-level neuroscience experimentations is shown. The capacity to excite sub-cellular compartments is demonstrated and an example utility to fast map variability in dendrites conductance is shown. The outcomes of this thesis present an outline and a first proof-of-concept for a future photogenetic retinal prosthesis. In addition, they provide the emerging optogenetic technology with a detailed analysis of its temporal resolution and a tool to expand its spatial resolution, which can have immediate high impact applications in modulating the activity of sub-cellular compartments, mapping neuronal networks and studying synchrony and plasticity effects.