title: Subretinal electrical stimulation reveals intact network activity in the blind mouse retina.
abstract: Retinal degeneration (rd) leads to progressive photoreceptor cell death, resulting in vision loss. Stimulation of the inner-retinal neurons by neuroprosthetic implants is one of the clinically approved vision-restoration strategies, providing basic visual percepts to blind patients. However, little is understood as to what degree the degenerating retinal circuitry and the resulting aberrant hyperactivity may prevent the stimulation of physiological electrical activity. Therefore, we electrically stimulated ex vivo retinas from wild-type (wt; C57BL/6J) and blind (rd10 and rd1) mice using an implantable subretinal microchip and simultaneously recorded and analyzed the retinal ganglion cell (RGC) output with a flexible microelectrode array. We found that subretinal anodal stimulation of the rd10 retina and wt retina evoked similar spatiotemporal RGC-spiking patterns. In both retinas, electrically stimulated ON and a small percentage of OFF RGC responses were detected. The spatial selectivity of the retinal network to electrical stimuli reveals an intact underlying network with a median receptive-field center of 350 μm in both retinas. An antagonistic surround is activated by stimulation with large electrode fields. However, in rd10 and to a higher percentage, in rd1 retinas, rhythmic and spatially unconfined RGC patterns were evoked by anodal or by cathodal electrical stimuli. Our findings demonstrate that the surviving retinal circuitry in photoreceptor-degenerated retinas is preserved in a way allowing for the stimulation of temporally diverse and spatially confined RGC activity. Future vision restoration strategies can build on these results but need to avoid evoking the easily inducible rhythmic activity in some retinal circuits.
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany; and Graduate School of Neural and Behavioural Sciences/International Max Planck Research School, Tübingen, Germany.
authors.forename: Henrike
authors.initials: H
authors.lastname: Stutzki
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany; and.
authors.forename: Florian
authors.initials: F
authors.lastname: Helmhold
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany; and.
authors.forename: Max
authors.initials: M
authors.lastname: Eickenscheidt
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany; and guenther.zeck@nmi.de.
authors.forename: Günther
authors.initials: G
authors.lastname: Zeck
mesh_terms: D000200:Action Potentials; D000818:Animals; D001766:Blindness / Q000503:physiopathology* / Q000628:therapy; D004195:Disease Models, Animal; D004558:Electric Stimulation; D058542:Implantable Neurostimulators; D008297:Male; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000503:physiopathology; D010507:Periodicity; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D012162:Retinal Degeneration / Q000503:physiopathology / Q000628:therapy; D012165:Retinal Ganglion Cells / Q000502:physiology*; D046509:Tissue Culture Techniques
keywords: neuroprosthetic stimulation; photoreceptor degeneration; retinal network