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Understanding properties of network-mediated responses elicited by epiretinal stimulation

Maesoon Im1,2
1Center for BioMicrosystems, Brain Science Institute,
Korea Institute of Science and Technology (KIST), Seoul, South Korea
2Division of Bio-Medical Science & Technology, KIST School,
University of Science and Technology (UST), Seoul, South Korea

Microelectronic retinal prostheses have restored a somewhat useful level of artificial vision in individuals blinded by outer retinal degenerative diseases. Despite impressive clinical outcomes, the restored vision is still far removed from the normal vision. To improve the quality of artificial vision, retinal prostheses are required to mimic several central features of visually-evoked responses in the healthy retina. Regarding this matter, I will cover the following three topics during this talk.
First, the eventual goal of retinal implant is to duplicate physiological signaling patterns that arise during natural viewing. However, this is extremely challenging because spiking patterns of retinal ganglion cells (RGCs) are remarkably heterogeneous even in a given type. It has long been thought that subretinal stimulation would be more advantageous than epiretinal one to use uniquely complex presynaptic networks in each RGC for network-mediated responses resembling their physiological responses. But, this premise had not been well validated. In our previous study using the healthy rabbit retinas, we demonstrated both epi- and sub-retinal stimulation can elicit highly similar network-mediated responses in a given RGC. Interestingly, those epiretinally-evoked network-mediated responses were closer match to visually-evoked responses in ON than OFF types.
Second, in the normal vision, ON and OFF cells covering a given visual space do not transmit neural signals to the downstream visual pathway because the brightness of the given visual space would not be increased and decreased at the same time. However, differential activation of ON or OFF types of RGCs has long been another key challenge in the field of retinal prosthetics. In a series of studies, we reported that optimal stimulation parameters (e.g. stimulation rate, stimulus duration/amplitude and stimulus waveform) can enhance the selectivity of ON over OFF types to better emulate exclusive firing of the two types.
Lastly, RGC responses to visual stimuli are known to be highly reproducible across repeats of an identical stimulus. I will briefly introduce our recent longitudinal study using rd10 mice about how retinal degeneration gradually alters the reproducibility of network-mediated responses. A systematic understanding of the change of RGC responses depending on the level of degeneration would offer some clinical insights.

Financial disclosure: None

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