Expression of Channelrhodopsin-2 in Rod Bipolar Cells Restores ON and OFF Responses at High Spatial Resolution in Blind Mouse Retina

Abstract

Rod bipolar cells (rBCs) represent a promising target for vision restoration as they relay information to the major image processing pathways in the retina. However, the diversity of the retinal output and the resolution obtained by optogenetic actuation of rBCs is unclear. Herein, the photostimulation of rBCs expressing channelrhodopsin-2 is studied in a transgenic, photoreceptor-degeneration mouse (rd10) while simultaneously recording the retinal output using a high-density microelectrode array. After analyzing several hundred retinal output neurons, both optogenetic ON and OFF type responses are identified at similar ratio at stimulation thresholds well below photodamage intensity. The temporal latency of both response types is in the same range ((Formula presented.) 50 ms) as reported for healthy mouse retinal ganglion cells. The spatial resolution ranges between 0.1 and 0.2 cycles deg-1, which is close to that found in healthy mice. Photostimulation over an extended area (29 deg) but not localized stimuli induces strong bursting activity, which may originate from large-scale activation of a coupled network of retinal cells. The distinct ON and OFF optogenetically induced activity patterns in retinal ganglion cells and the high temporal and spatial resolution demonstrate that near-physiological vision restoration may be achieved under optimal conditions in late stage retinal degeneration.