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

Inayat, Samsoon; Rountree, Corey M.; Troy, John B.; Saggere, Laxman

doi:10.1088/1741-2560/12/1/016010

Cited by 23 publications

(46 citation statements)

References 77 publications

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“…PSTHs were further analyzed by extracting the temporal characteristics of spike rate responses including the time width and response latency. The time width of responses was calculated as the width at half maximum amplitude while the response latency was determined to be the first time point of the width 14 . These analyses were performed on RGC response data corresponding to both chemical and visual stimulation to facilitate comparisons of the spike rate temporal characteristics.…”

Section: Methodsmentioning

confidence: 99%

“…Both the patterned responses of RGCs and spatial localization of glutamate stimulation were investigated by mapping the locations of glutamate-responsive RGCs exhibiting somal spike shapes using the vectors separating electrodes recording responsive units from the glutamate injection sites. Units exhibiting somal, as opposed to axonal, spike shapes were specifically utilized since they are more closely colocalized with glutamate receptors (for details see Inayat et al 14 ), the intended primary targets of this neurotransmitter stimulation. For each stimulation pattern, these vectors were assembled into a 2D histogram via spatial binning to represent the approximate locations of electrodes where responsive RGCs were recorded.…”

Section: Methodsmentioning

confidence: 99%

“…An artificial chemical synapse chip would use exogenous neurotransmitter(s) to biomimetically stimulate the surviving retinal neurons of a degenerated retina through the same synaptic pathways used by normal vision. The feasibility of neurotransmitterbased stimulation of the retina in both epiretinal and subretinal configurations has been recently established through in vitro studies wherein glutamate, the primary neurotransmitter in the retina, was injected into explanted retinas at isolated single sites through single-port micropipettes [12][13][14] . While these single-site glutamate stimulation studies have shown that glutamate can be effective and advantageous over electrical current in achieving high spatial resolutions, multisite patterned stimulation of the retina with glutamate, which is critical for translating two-dimensional visual images into afferent neural signals to accomplish complex visual tasks such as navigation and reading, has never been demonstrated before.…”

Section: Introductionmentioning

confidence: 99%

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Prototype chemical synapse chip for spatially patterned neurotransmitter stimulation of the retina ex vivo

et al. 2017

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Biomimetic stimulation of the retina with neurotransmitters, the natural agents of communication at chemical synapses, could be more effective than electrical stimulation for treating blindness from photoreceptor degenerative diseases. Recent studies have demonstrated the feasibility of neurotransmitter stimulation by injecting glutamate, a primary retinal neurotransmitter, into the retina at isolated single sites. Here, we demonstrate spatially patterned multisite stimulation of the retina with glutamate, offering the first experimental evidence for applicability of this strategy for translating visual patterns into afferent neural signals. To accomplish pattern stimulation, we fabricated a special microfluidic device comprising an array of independently addressable microports connected to tiny on-chip glutamate reservoirs via microchannels. The device prefilled with glutamate was interfaced with explanted rat retinas placed over a multielectrode array (MEA) with the retinal ganglion cells (RGC) contacting the electrodes and photoreceptor surface contacting the microports. By independently and simultaneously activating a subset of the microports with modulated pressure pulses, small boluses of glutamate were convectively injected at multiple sites in alphabet patterns over the photoreceptor surface. We found that the glutamate-driven RGC responses recorded through the MEA system were robust and spatially laid out in patterns strongly resembling the injection patterns. The stimulations were also highly localized with spatial resolutions comparable to or better than electrical retinal prostheses. Our findings suggest that surface stimulation of the retina with neurotransmitters in pixelated patterns of visual images is feasible and an artificial chemical synapse chip based on this approach could potentially circumvent the limitations of electrical retinal prostheses.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prototype chemical synapse chip for spatially patterned neurotransmitter stimulation of the retina ex vivo

et al. 2017

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“…A neurotransmitter chemical, particularly glutamate, the main agent of intercellular communication in the normal retina, has long been suggested as a more effective stimulus agent than electrical current for a retinal prosthesis, though very few studies have explored the feasibility of retinal stimulation with neurotransmitters15161718. Two studies1718 that have demonstrated the feasibility of glutamate stimulation of in-vitro preparations of whole retinas focused on direct stimulation of RGCs from the epiretinal side.…”

mentioning

confidence: 99%

“…Two studies1718 that have demonstrated the feasibility of glutamate stimulation of in-vitro preparations of whole retinas focused on direct stimulation of RGCs from the epiretinal side. These studies showed glutamate to be effective and advantageous over electrical current in stimulating RGCs, but since they bypassed INL neurons, they did not take advantage of the intrinsic visual processing capability of INL circuitry.…”

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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Multidisciplinary Approaches in the Treatment of Retinal Degenerative Diseases: A Review

Chen,

Zhuo,

Zhu

et al. 2023

Advanced Therapeutics

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Retinal degenerative diseases (RDDs) cause irreversible blindness and affect ≈285 million individuals worldwide. The unavailability of treatment to stop the progression of RDDs or restore normal visual function necessitated development of novel therapeutic strategies. In recent years, multidisciplinary approaches have shown great potential for the treatment of RDDs, including intraocular delivery systems, retinal scaffolds for cell therapy, and visual prostheses with different stimulation strategies. This review focuses on the development prospects and shortcomings of various multidisciplinary treatment approaches for RDDs. The results of this review will hopefully inspire further innovation in the design of novel multidisciplinary approaches for RDD treatment and accelerate their commercialization.

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

Cited by 23 publications

References 77 publications

Prototype chemical synapse chip for spatially patterned neurotransmitter stimulation of the retina ex vivo

Prototype chemical synapse chip for spatially patterned neurotransmitter stimulation of the retina ex vivo

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

Multidisciplinary Approaches in the Treatment of Retinal Degenerative Diseases: A Review

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