of visual pathways (e.g. ON and OFF channels) within the visual system. Thus, at this point, electricity cannot encode important sensory features used in normal central visual processing.

9.4.2  Requirements and Benefits of Neurotransmitter

Stimulation

Many of these limitations could be circumvented by using more naturalistic means of stimulating retinal ganglion cells (RGCs) for a retinal prosthesis. Natural vision is encoded as neurotransmitter signals. Neurotransmitter-based retinal prosthesis designs will enable us to design and build a device based upon the physiological requirements for RGC stimulation by exogenous neurotransmitters in retinal degeneration. Our preliminary results show that glutamate is effective in stimulating retinal ganglion cells. RGC responses to exogenously applied glutamate are brief, since excitatory amino acid transmitter transporter systems (EAATs) rapidly remove glutamate from the extracellular space. A neurotransmitter-based retinal prosthesis could also take advantage of other transmitters, simultaneously. For example, OFF responses may be mimicked by applying inhibitory transmitters such as glycine or GABA. By applying these inhibitory neurotransmitters adjacent to areas of glutamate stimulation, we may be able to simulate visual contrast. This approach is not possible with electrical stimulation alone. Finally, effective prostheses may use both transmitter and electrical stimulation, synergistically. However, the parameters for stimulating RGCs using glutamate and other neurotransmitters in diseased retinas have not been established.

9.5  Technical Considerations and Design Approaches

9.5.1  Operating Principles for a Neurotransmitter-Based Retinal Prosthesis

Retinal prosthetic devices produce artificial vision by replacing the function of photoreceptors lost due to retinal degeneration. Ideally, these devices pattern afferent stimulation to the remaining retinal neurons, in spatially and temporally naturalistic patterns. Electrically based retinal prosthetic devices initiate neuronal stimulation by inducing local electrical fields that activate voltage-gated ion channels. Neurotransmitter-based devices are capable of directly stimulating or inhibiting neurons by selectively activating ligand-gated ion channels. This requires stimulation hardware capable of accurately modulating the localized delivery of neurotransmitters in space and time. While microelectronic circuitry for the control of release has evolved considerably over many decades, methods for delivering neurotransmitters with these devices are still within relatively early stages of development.