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Kinetics of the bipolar cell response to electrical stimulation: computational modeling

Institute for Analysis and Scientific Computing, Vienna University of Technology, Vienna, Austria
Department of Ophthalmology and Hansen Experimental Physics Laboratory, Stanford University, CA

Purpose: To restore sight in atrophic age-related macular degeneration, the lost photoreceptors can be replaced with electronic implants, which replicate their two major functions: converting light into electric signal and transferring visual information to the secondary neurons in the retinal neural network – the bipolar cells (BC). We study the selectivity of BC activation by subretinal implants and dynamics of their response to pulsatile waveforms in order to optimize the electrical stimulation scheme such that retinal signal processing with “electronic photoreceptors” remains as close to natural as possible.

Methods: Electric field was computed for various electrode configurations in a 3-d finite element model. A multicompartmental model of BC was implemented to simulate responses of the voltage-gated calcium channels and subsequent synaptic vesicle release under continuous and pulsatile stimuli. We compared the predicted response under various frequencies, pulse durations, and alternating gratings to the corresponding experimental measurements.

Results: The modeled BC-mediated retinal responses were in good agreement with previously published experimental results. Kinetics of the calcium pumps and of the neurotransmitter release in ribbon synapses, which underpin the BC’s temporal filtering and rectifying functions, allow mimicking the natural BC response with high frequency pulsatile stimulation, thereby preserving such features of the retinal signal processing as flicker fusion, adaptation to static stimuli and non-linear summation of subunits in receptive field. Selectivity of the BC stimulation while avoiding direct activation of the downstream neurons (amacrine and ganglion cells - RGCs) is improved with local return electrodes.

Conclusions: If the retinal neural network is preserved to a large extent in age-related macular degeneration, selective stimulation of BCs with proper spatial and temporal modulation of the extracellular electric field may retain many features of the natural retinal signal processing and hence allow highly functional restoration of sight.

Financial disclosure: DP: Pixium Vision - Consultant (C) and Patents (P)

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