Neurotransmitter Stimulation for Retinal Prosthesis: The Artificial Synapse Chip

Iezzi, Raymond; Finlayson, Paul G.

doi:10.1007/978-1-4419-0754-7_9

Cited by 12 publications

(18 citation statements)

References 103 publications

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“…Our prior work in mathe- matically modeling glutamate concentrations necessary for spiketrain responses identified that synaptic concentrations of glutamate between 0.5 and 11 mM would be necessary. 31 This finding is consistent with those in the present study.…”

Section: Discussionsupporting

confidence: 94%

Glutamate Stimulation of Retinal Ganglion Cells in Normal and S334ter-4 Rat Retinas: A Candidate for a Neurotransmitter-Based Retinal Prosthesis

Finlayson

Iezzi

2010

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To investigate the suitability of glutamate as a potential agent for a neurotransmitter-based retinal prosthesis. METHODS. Retinal ganglion cells (RGCs) from P35-70 albino Sprague-Dawley (normal) and P60-254 S334ter-4 (photoreceptor degeneration) rats were recorded extracellularly in flattened eye cup preparations, to assess their responses to glutamate, applied locally via micropipettes. RESULTS. Brief local application of glutamate effectively excited RGCs in both normal and degenerated retinas. Epiretinal surface application of glutamate was less likely to excite RGCs than was subsurface application (20 microm below the epiretinal surface). Glutamate evoked RGC firing rates, and the response patterns were similar for epiretinal surface and subsurface applications. Subsurface application of 2 mM glutamate effectively excited cells within 130 microm of the ejection sites. Response latencies averaged 281 ms and were significantly longer for OFF RGCs than for ON RGCs in normal retinas (P = 0.025). Suppression of activity was observed at shorter latencies ( approximately 100 ms) after glutamate application in most of the spontaneously active RGCs. Responses to each glutamate application were similar, and the duration of activity was directly dependent on the duration of application. RGC responses varied from recurrent high-frequency bursts to sustained firing at rates above 40 spikes/s, in normal and degenerated retinas. Paired, sequential applications of glutamate evoked two distinguishable responses, with interstimulus intervals as low as 200 ms. Overall, RGC response sensitivity to glutamate was similar in normal and degenerated retinas. CONCLUSIONS. Glutamate is an excellent candidate for a neurotransmitter-based retinal prosthesis, as its local application effectively stimulates RGCs with high spatial and temporal resolution.

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Section: Discussionsupporting

confidence: 94%

Glutamate Stimulation of Retinal Ganglion Cells in Normal and S334ter-4 Rat Retinas: A Candidate for a Neurotransmitter-Based Retinal Prosthesis

Finlayson

Iezzi

2010

Invest. Ophthalmol. Vis. Sci.

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“…Theorizing that the loss of glutamate sensitivity is likely caused by the lack of glutamatergic input from PRs, these studies suggest that early therapeutic intervention of a degenerated retina could preserve glutamate sensitivity in INL neurons whereas treating late stage degeneration may be possible, albeit difficult. Based on this evidence, it has been hypothesized that subretinal glutamate stimulation of the INL of a degenerated retina could activate RGCs through the amacrine-bipolar-RGC pathway and allow for differential stimulation of the OFF and ON pathways of visual circuitry 24 . The possibility of activating RGCs through INL neurons has a paradigm-shifting implication for retinal prosthesis technology because this biomimetic stimulation of the retina could restore high resolution naturalistic vision to patients with PR degeneration.…”

Section: Introductionmentioning

confidence: 99%

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

Inayat

Jb³

et al. 2016

Preprint

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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

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“…Theorizing that the loss of glutamate sensitivity is likely caused by the lack of glutamatergic input from PRs, these studies suggest that early therapeutic intervention of a degenerated retina could preserve glutamate sensitivity in INL neurons whereas treating late stage degeneration may be possible, albeit difficult. Based on this evidence, it has been hypothesized that subretinal glutamate stimulation of the INL of a degenerated retina could activate RGCs through the amacrine-bipolar-RGC pathway and allow for differential stimulation of the OFF and ON pathways of visual circuitry26. The possibility of activating RGCs through INL neurons has a paradigm-shifting implication for retinal prosthesis technology because this biomimetic stimulation of the retina could restore high resolution naturalistic vision to patients with PR degeneration.…”

mentioning

confidence: 99%

Differential stimulation of the retina with subretinally injected exogenous neurotransmitter: A biomimetic alternative to electrical stimulation

Rountree

Inayat

Troy

et al. 2016

Sci Rep

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

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Neurotransmitter Stimulation for Retinal Prosthesis: The Artificial Synapse Chip

Cited by 12 publications

References 103 publications

Glutamate Stimulation of Retinal Ganglion Cells in Normal and S334ter-4 Rat Retinas: A Candidate for a Neurotransmitter-Based Retinal Prosthesis

Glutamate Stimulation of Retinal Ganglion Cells in Normal and S334ter-4 Rat Retinas: A Candidate for a Neurotransmitter-Based Retinal Prosthesis

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

Differential stimulation of the retina with subretinally injected exogenous neurotransmitter: A biomimetic alternative to electrical stimulation

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