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In search for optimal stimuli for retinal prosthetics

Günther Zeck and collaborators
Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany,
Purpose: To investigate the feasibility and benefits of smooth-wave stimuli for retinal prosthetics.

Methods: Time-continuous current waveforms were applied to ex vivo photoreceptor-degenerated mouse retina while simultaneously recording the modulated retinal ganglion cell activity using microelectrode arrays. First, the reliability of sinusoidal smooth wave stimuli and the electrical safety limits by monitoring the stimulation current.
Next, we searched for optimal stimuli based on two theoretical approaches: (i) Application of electrical temporal white noise stimuli and evaluation of the mean-effective stimuli based on LNP modelling [Höfling et al., Sci. Rep. 2020] and (ii) multi-compartment modelling of ON and OFF bipolar cell types towards selective activation using computed electric stimulus waveforms [Oesterle et al., bioRxiv 2020].

Results: Smooth-wave stimulation of retinal networks reliably evokes and modulates ganglion cells activity. Stimulation thresholds are within electrode safety limits, i.e. below 5 nC for 30 µm electrodes. The evoked spiking to temporal white noise stimuli shows a high reliability, which decreases with distance from the stimulation electrode. White noise stimuli reveal temporal filters, which can be separated in three clusters in healthy retina but not in adult, photoreceptor-degenerated retina.
Multi-compartmental modelling of bipolar cells has been optimized using data obtained from two-photon imaging of glutamate release by these cells and embedded in a simulation framework, taking into account stimulation currents. Distinct waveforms for one ON and one OFF bipolar cell type were derived.

Conclusions: Smooth-wave stimuli reliably activate retinal neurons, as inferred from the robust retinal ganglion cell spiking activity at activation thresholds well within safety limits. Waveforms estimated from white noise stimulation (epiretinal configuration) peaked a few milliseconds before spike, evoked reliable spiking but were not cell-type specific. Optimal waveforms estimated from multi-compartment modelling (subretinal configuration) suggest tri-phasic stimulation currents for the activation of OFF bipolar cells and bi-phasic shapes for the activation of ON bipolar cells. 

Financial disclosures: None

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