Abstract
Currently, the use of optogenetic sensitization of retinal cells combined with activation/inhibition has the potential to be an alternative to retinal implants that would require electrodes inside every single neuron for high visual resolution. However, clinical translation of optogenetic activation for restoration of vision suffers from the drawback that the narrow spectral sensitivity of an opsin requires active stimulation by a blue laser or a light emitting diode with much higher intensities than ambient light. In order to allow an ambient light-based stimulation paradigm, we report the development of a ‘white-opsin’ that has broad spectral excitability in the visible spectrum. The cells sensitized with white-opsin showed excitability at an order of magnitude higher with white light compared to using only narrow-band light components. Further, cells sensitized with white-opsin produced a photocurrent that was five times higher than Channelrhodopsin-2 under similar photo-excitation conditions. The use of fast white-opsin may allow opsin-sensitized neurons in a degenerated retina to exhibit a higher sensitivity to ambient white light. This property, therefore, significantly lowers the activation threshold in contrast to conventional approaches that use intense narrow-band opsins and light to activate cellular stimulation.
Highlights
Optogenetic stimulation provides high temporal precision [1,2,3,4,5,6], minimal invasiveness [7] and cellular specificity by introducing light-activatable ion-channels into cells by genetic targeting
The ultimate goal in using the broad spectrally-sensitive opsin described in this study is to enable ambient white-light (~0.01 mW/mm2) to restore vision lost in patients suffering from retinitis pigmentosa (RP) [28,29]
RP and age-related macular degeneration (AMD) are diseases characterized by marked degeneration of retinal photoreceptors, which hinder vision through a lack of light-dependent neuronal activation and a cessation of signal transmission to the visual cortex [29,30,31,32]
Summary
Optogenetic stimulation provides high temporal precision [1,2,3,4,5,6], minimal invasiveness [7] and cellular specificity by introducing light-activatable ion-channels into cells by genetic targeting. The use of optogenetic sensitization of retinal cells, combined with active light stimulation, has allowed the possibility of eliminating the requirement of placing electrodes near the retina. This optogenetic activation method is very promising as it only requires light of moderate intensity (~0.1 mW/mm2) that can be delivered from a light emitting diode (LED) or laser [1,2]. Clinical translation of optogenetic activation for visual restoration suffers from the use of microbial opsins that possess narrow spectral sensitivities and narrow-band active excitation sources. All attempts for PLOS ONE | DOI:10.1371/journal.pone.0136958 September 11, 2015
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