Abstract
Subretinal prostheses are designed to restore sight in patients blinded by retinal degeneration using electrical stimulation of the inner retinal neurons. To relate retinal output to perception, we studied behavioral thresholds in blind rats with photovoltaic subretinal prostheses stimulated by full-field pulsed illumination at 20 Hz, and measured retinal ganglion cell (RGC) responses to similar stimuli ex-vivo. Behaviorally, rats exhibited startling response to changes in brightness, with an average contrast threshold of 12%, which could not be explained by changes in the average RGC spiking rate. However, RGCs exhibited millisecond-scale variations in spike timing, even when the average rate did not change significantly. At 12% temporal contrast, changes in firing patterns of prosthetic response were as significant as with 2.3% contrast steps in visible light stimulation of healthy retinas. This suggests that millisecond-scale changes in spiking patterns define perceptual thresholds of prosthetic vision. Response to the last pulse in the stimulation burst lasted longer than the steady-state response during the burst. This may be interpreted as an excitatory OFF response to prosthetic stimulation, and can explain behavioral response to decrease in illumination. Contrast enhancement of images prior to delivery to subretinal prosthesis can partially compensate for reduced contrast sensitivity of prosthetic vision.
Highlights
Retinal degenerative diseases are the leading cause of untreatable blindness
Sighted rats (LE) with photovoltaic implants did not respond to stimulation either, suggesting that normal vision in our experimental paradigm dominates the small prosthetic input[21], and thereby eliminates the startling response observed in blind animals lacking any additional visual information
Since this perceptual threshold was measured without discriminating between the ON and OFF contrast steps, it corresponds to the highest sensitivity curve in ex-vivo measurements, which was a response to positive contrast steps
Summary
Retinal degenerative diseases are the leading cause of untreatable blindness. Age-related macular degeneration alone affects 8.7% of population worldwide, and the number is projected to reach 196 million by 2020 and 288 million by 20401. Epiretinal prostheses typically target the retinal ganglion cells (RGC)[6], improved phosphene localization has been reported with activation of the inner retina using longer pulses[7]. Subretinal implants stimulate the inner retinal neurons (primarily bipolar cells), and rely on the retinal network to transmit their responses to RGCs8. Both types of implants have been approved for clinical testing[9,10], but current systems are powered by extra-ocular electronics, and require trans-scleral cables and complex surgeries. Patients implanted with subretinal prostheses report patterned percepts of light, called phosphenes, following electrical activation of the inner retinal layer[9,16] but little is known about the neural mechanisms mediating perception of prosthetic vision. We revisited the measurements of contrast sensitivity ex-vivo using a novel analysis of the firing patterns, rather than simple spike counting, and observed contrast sensitivity in closer agreement with behavioral measurements
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