Broadband activation by white-opsin lowers intensity threshold for cellular stimulation.

Subrata Batabyal,David Birch,Gregory Cervenka,Young-Tae Kim,Samarendra Mohanty

doi:10.1038/srep17857

Subrata Batabyal, David Birch + Show 3 more

Open Access

https://doi.org/10.1038/srep17857

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Abstract

Photoreceptors, which initiate the conversion of ambient light to action potentials via retinal circuitry, degenerate in retinal diseases such as retinitis pigmentosa and age related macular degeneration leading to loss of vision. Current prosthetic devices using arrays consisting of electrodes or LEDs (for optogenetic activation of conventional narrow-band opsins) have limited spatial resolution and can cause damage to retinal circuits by mechanical or photochemical (by absorption of intense narrow band light) means. Here, we describe a broad-band light activatable white-opsin for generating significant photocurrent at white light intensity levels close to ambient daylight conditions. White-opsin produced an order of magnitude higher photocurrent in response to white light as compared to narrow-band opsin channelrhodopsin-2, while maintaining the ms-channel kinetics. High fidelity of peak-photocurrent (both amplitude and latency) of white-opsin in response to repetitive white light stimulation of varying pulse width was observed. The significantly lower intensity stimulation required for activating white-opsin sensitized cells may facilitate ambient white light-based restoration of vision for patients with widespread photoreceptor degeneration.

Highlights

Photoreceptors, which initiate the conversion of ambient light to action potentials via retinal circuitry, degenerate in retinal diseases such as retinitis pigmentosa and age related macular degeneration leading to loss of vision
The disadvantages of retinal implants include chronic damage from the implanted electrodes, insufficient current produced by microphotodiode from the ambient light to stimulate adjacent neurons[13,14], cellular outgrowth due to surgical implantation, and disordered stimulation patterns resulting from the electrical stimulation of both the axon and soma[14]
Optogenetic activation of ChR2 has been evaluated for vision restoration in mice models of retinal degeneration either by non-specific stimulation of retina[22] or in a cell-specific manner for retinal ganglion cells[23,24,25,26,27] and ON bipolar cells[28,29]

Summary

Introduction

Photoreceptors, which initiate the conversion of ambient light to action potentials via retinal circuitry, degenerate in retinal diseases such as retinitis pigmentosa and age related macular degeneration leading to loss of vision. Optogenetic sensitization (e.g. channelrhodopsin-2, ChR2; halorhodopsin, NpHR) of higher-order retinal neurons or residual receptors, and cell-specific activation/inhibition with high temporal precision[15,16,17,18,19] has potential as an alternative to electrical stimulation through implants Optogenetics has advantages such as cellular specificity (e.g. residual cones, ganglion or bipolar cells), minimal invasiveness[20,21] and elimination of intraocular surgery. The significantly reduced white light stimulation intensity required for activating white-opsin sensitized cells will lead to ambient white light based restoration of vision in case of retinal degenerative diseases. This will provide high resolution vision restoration and eliminate the requirement of active-stimulation device

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