Manipulation of RGCs Response Using Different Stimulation Strategies for Retinal Prosthesi

Retinal prosthetic implants have shown potential to restore partial vision to patients blinded by retinitis pigmentosa or dry age-related macular degeneration, via a camera-driven multielectrode array that electrically stimulates surviving retinal neurons. To analyze the effectiveness of these implants, single-unit or multielectrode recordings of neurons from isolated animal retina are commonly used. However, such electrical recording methods are strongly affected by stimulation artifact and limited in terms of the spatial patterns of retinal activation. Virus-transduced calcium indicators are effective reporters of neural activity, offering the advantage of cell-specific labeling. To track the time dependence of in vivo expression levels of genetically encoded calcium indicators (GECIs) in rodent retina, we developed a noninvasive imaging approach based on a custom-modified, low-cost and simple fundus system that enabled us to monitor and characterize in vivo bright-field and fluorescence retinal image, further evaluating in vivo fluorescence reporter expression. Commercial epi-retinal prostheses mostly use charge-balanced symmetric cathodic-first biphasic pulses to depolarize retinal ganglion cells (RGCs) and bipolar cells (BCs), resulting in the perception of light in blind patients. However, previous clinical study for patients with Argus II epiretinal implants reported most percepts evoked by single electrode stimulation were elongated and aligned with estimated axon path of retinal ganglion cells, suggesting the activation of axon bundles. Based on the established in vitro calcium imaging and electrophysiological animal model, we performed in vitro calcium imaging for different stimulation paradigms, focusing primarily on short duration pulse with different types of waveform and current steering method that can avoid axonal stimulation and manipulate the thresholds of targeted RGC somas. The findings support the possibility to manipulate the responses of RGCs through varying the stimulation waveform or return electrodes, thus potentially forming more ideal shape perception with higher spatial resolution in future retinal prosthesis design.