Abstract
Purpose :
Achieving locally selective stimulation of the retinal ganglion cell (RGC) layer remains one of the major factors limiting the quality of percepts evoked in patients implanted with epiretinal devices. Photovoltaic prostheses based on organic semiconductors offer the possibility of standalone stimulation at high spatial resolution, with a remarkable increase in retinal coverage and pixels density. Here we inquired, using an hybrid experimental-computationnal approach, whether and why a photovoltaic epiretinal paradigm could elicit targeted responses in the RGC layer.
Methods :
We fabricated a wide-field retinal prosthesis based on a polydimethylsiloxane flexible substrate embedding photovoltaic pixels made of conjugated polymers; and tested its ability to stimulate explanted retinal degeneration 10 retinal circuits at advanced stages of degeneration. From single-unit extracellular recordings, we performed quantitative and spatial analysis of RGCs responses to photovoltaic and electrical stimulation. Pixels miniaturization and densification, voltage waveform and pulse duration were taken heed of. Inner non-spiking cells activities were assessed using a biophysical model of the retinal tissue.
Results :
Full field as single pixel illumination generated direct and network-mediated activities in RGCs. While the direct response was exposure insensitive, the pulse lengthening strengthened indirect response up to 44 ± 7.4 % of its initial value in the range of tested durations. Inner retinal network activity modelling revealed that both bipolar and amacrine (AC) cells are necessary to engender indirect activity patterns. Electrical stimulation with capacitive-like pulses as delivered at the pixels interface caused sustained interneurons depolarization, thus leading to an indirect activity 66.6 ± 11.7 % higher than the one evoked with rectangular pulses. The recruitment of the AC layer can be correlated to the focusing of response in RGCs.
Conclusions :
Indirect epiretinal stimulation of RGCs, through long or non-rectangular voltage pulses, promises to be an efficient alternative strategy to overcome current resolution challenges. Our approach based on the combination of a dense freestanding array of photovoltaic pixels allowing single pixel activation of RGC layer, together with stimulation parameters favouring natural lateral inhibition, provides a significant improvement towards high-resolution prosthetic vision.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.