Differential stimulation of the retina with glutamate toward a neurotransmitter-based retinal prosthesis

Abstract

13Subretinal stimulation of the retina with neurotransmitters, the normal means of conveying visual 14 information, is a potentially better alternative to electrical stimulation widely used in current retinal 15 prostheses for treating blindness from photoreceptor degenerative diseases. Yet, no retinal 16 stimulation study exploiting the inner retinal pathways exists. Here, we demonstrate the feasibility 17 of differentially stimulating retinal ganglion cells (RGCs) through the inner nuclear layer of the 18 retina with glutamate, a primary neurotransmitter chemical, in a biomimetic way. We show that 19 controlled pulsatile delivery of glutamate into the subsurface of explanted wild-type rat retinas 20 elicits highly localized simultaneous inhibitory and excitatory spike rate responses in OFF and ON 21 RGCs. We also present the spatiotemporal characteristics of RGC responses to subretinally 22 injected glutamate and the therapeutic stimulation parameters. Our findings could pave the way 23 for future development of a neurotransmitter-based subretinal prosthesis offering more 24 naturalistic vision and better visual acuity than electrical prostheses.25

Chemical stimulation of rat retinal neurons: feasibility of an epiretinal neurotransmitter-based prosthesis

“…Electrical stimulation also activates both somata and axons, degrading spatial resolution. Chemical stimulation of retinal neurons through exogenous neurotransmitters is an approach which avoids these problems and might offer a better solution [19,22,23,36,37]. The design of a neurotransmitter-based retinal prosthesis primarily requires exploration of stimulation parameters (type of neurotransmitter, its concentration, volume, and flow rate) that will elicit a spiking response in RGCs and how these parameters affect response characteristics (amplitude, latency, spread, and temporal properties) of various RGC subtypes.…”

Neuromodulation using electroosmosis

“…The excitatory spike rate amplitude, latency and response time width scaled as expected with different EOF actuation voltages. EOF injections had similar latencies (90 ms compared to 70 [17] and 75 ms [38]) to the prior work with pneumatic activation, and comparable spike rate amplitudes and time-widths. We postulate that the stimulation latencies with EOF injections were a combination of two phenomena: (a) latency between the input command signal and EOF onset from the micropipette tip (T1 latencies in section 2.3), and (b) the excitation latency of RGCs [7,8,18].…”

“…Subretinal chemical stimulation seeks to substitute for glutamate release characteristic of the lost PRs in a PR degenerated retina. Progressive morphological changes in the retina and neural connections are observed at various stages of PR degeneration [35][36][37], and subretinal chemical stimulation is found to be consistently effective at these various stages [38]. Chemical stimulation has the potential to provide high spatial resolution for artificial vision since the chemical injecting ports can be arranged in a dense array [18,39].…”

“…With electrical stimulation, however, there is risk of electrochemically induced tissue damage [14,34,40,41] as electrode packing increases and the stimulation electrode area is reduced. The above noted foundational studies in chemical retinal stimulation [8,[16][17][18]38] used a commercially available external pressure injector to drive glutamate release pneumatically to evoke neural responses from retinal cells in-vitro. However, to transition chemical stimulation from in-vitro to in-vivo implementation, there is a need to develop a device with implant specific characteristics such as a microscale footprint, onboard power supply and an incorporated neurotransmitter actuation system.…”

Photothermal liquid release from arrayed Au nanorod/hydrogel composites for chemical stimulation

“…Biomimetic stimulations of the retina with neurotransmitters are also demonstrated. A chemical synapse chip with eight microfluidic ports was proposed to deliver spatially patterned neurotransmitter ejection [10].…”