title: Chemical stimulation of rat retinal neurons: feasibility of an epiretinal neurotransmitter-based prosthesis.
abstract: OBJECTIVE
  No cure currently exists for photoreceptor degenerative diseases, which cause partial or total blindness in millions of people worldwide. Electrical retinal prostheses have been developed by several groups with the goal of restoring vision lost to these diseases, but electrical stimulation has limitations. It excites both somas and axons, activating retinal pathways nonphysiologically, and limits spatial resolution because of current spread. Chemical stimulation of retinal ganglion cells (RGCs) using the neurotransmitter glutamate has been suggested as an alternative to electrical stimulation with some significant advantages. However, sufficient scientific data to support developing a chemical-based retinal prosthesis is lacking. The goal of this study was to investigate the feasibility of a neurotransmitter-based retinal prosthesis and determine therapeutic stimulation parameters.
  
  
  METHODS
  We injected controlled amounts of glutamate into rat retinas from the epiretinal side ex vivo via micropipettes using a pressure injection system and recorded RGC responses with a multielectrode array. Responsive units were identified using a spike rate threshold of 3 Hz.
  
  
  RESULTS
  We recorded both somal and axonal units and demonstrated successful glutamatergic stimulation across different RGC subtypes. Analyses show that exogenous glutamate acts on RGC synapses similar to endogenous glutamate and, unlike electrical prostheses, stimulates only RGC somata. The spatial spread of glutamate stimulation was ≈ 290 μm from the injection site, comparable to current electrical prostheses. Further, the glutamate injections produced spatially differential responses in OFF, ON, and ON-OFF RGC subtypes, suggesting that differential stimulation of the OFF and ON systems may be possible. A temporal resolution of 3.2 Hz was obtained, which is a rate suitable for spatial vision.
  
  
  CONCLUSIONS
  We provide strong support for the feasibility of an epiretinal neurotransmitter-based retinal prosthesis. Our findings suggest that chemical stimulation of RGCs is a viable alternative to electrical stimulation and could offer distinct advantages such as the selective stimulation of RGC somata.
authors.affiliation: Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, Illinois, USA. Department of Neurobiology, Northwestern University, Evanston, Illinois, USA.
authors.forename: Samsoon
authors.initials: S
authors.lastname: Inayat
authors.forename: Corey M
authors.initials: CM
authors.lastname: Rountree
authors.forename: John B
authors.initials: JB
authors.lastname: Troy
authors.forename: Laxman
authors.initials: L
authors.lastname: Saggere
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D000818:Animals; D005240:Feasibility Studies; D018698:Glutamic Acid / Q000008:administration & dosage; D008027:Light; D018377:Neurotransmitter Agents / Q000008:administration & dosage*; D010719:Phosphenes / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D010775:Photic Stimulation / Q000379:methods; D051381:Rats; D020318:Rats, Long-Evans; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013268:Stimulation, Chemical; D057488:Visual Prosthesis
chemical_list: D018377:Neurotransmitter Agents; D018698:Glutamic Acid