title: Differential stimulation of the retina with subretinally injected exogenous neurotransmitter: A biomimetic alternative to electrical stimulation.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Corey M
authors.initials: CM
authors.lastname: Rountree
authors.affiliation: Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
authors.forename: Samsoon
authors.initials: S
authors.lastname: Inayat
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Troy
authors.affiliation: Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
authors.forename: Laxman
authors.initials: L
authors.lastname: Saggere
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D004558:Electric Stimulation; D005074:Evoked Potentials, Visual / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000008:administration & dosage; D007267:Injections; D008297:Male; D018377:Neurotransmitter Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D012160:Retina / Q000187:drug effects*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects; D013997:Time Factors
chemical_list: D018377:Neurotransmitter Agents; D018698:Glutamic Acid