Interaction between native and prosthetic visual responses in optogenetic visual restoration
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American Society for Clinical Investigation
Abstract
Degenerative retinal disorders leading to irreversible photoreceptor death are a common cause of
blindness. Optogenetic gene therapy aims to restore vision in affected individuals by introducing
light-sensitive opsins into the surviving neurons of the inner retina. While up until now, the main
focus of optogenetic therapy has been on terminally blind individuals, treating at stages where
residual native vision is present could have several advantages. However, it is still unknown how
residual native and optogenetic vision would interact if present at the same time. Using transgenic
mice expressing the optogenetic tool ReaChR in ON-bipolar cells, we herein examine this interaction
through electroretinography (ERG) and visually evoked potentials (VEP). We find that optogenetic
responses show a peculiar ERG signature and are enhanced in retinas without photoreceptor
loss. Conversely, native responses are dampened in the presence of ReaChR. Moreover, in VEP
recordings, we find that optogenetic responses reach the cortex asynchronous to the native
response. These findings should be taken into consideration when planning future clinical trials and
may direct future preclinical research to optimize optogenetic approaches for visual restoration. The
identified ERG signatures, moreover, may serve to track treatment efficiency in clinical trials.
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Except where otherwised noted, this item's license is described as Attribution 4.0 International
