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Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration
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Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration
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Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration
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Journal Article
Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration
2008
Overview
Genetically encoded optical neuromodulators create an opportunity for circuit-specific intervention in neurological diseases. One of the diseases most amenable to this approach is retinal degeneration, where the loss of photoreceptors leads to complete blindness. To restore photosensitivity, we genetically targeted a light-activated cation channel, channelrhodopsin-2, to second-order neurons, ON bipolar cells, of degenerated retinas
in vivo
in the
Pde6b
rd1
(also known as
rd1
) mouse model. In the absence of 'classical' photoreceptors, we found that ON bipolar cells that were engineered to be photosensitive induced light-evoked spiking activity in ganglion cells. The rescue of light sensitivity was selective to the ON circuits that would naturally respond to increases in brightness. Despite degeneration of the outer retina, our intervention restored transient responses and center-surround organization of ganglion cells. The resulting signals were relayed to the visual cortex and were sufficient for the animals to successfully perform optomotor behavioral tasks.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animals
/ Biomedical and Life Sciences
/ Evoked Potentials, Visual - drug effects
/ Evoked Potentials, Visual - physiology
/ Evoked Potentials, Visual - radiation effects
/ Excitatory Amino Acid Antagonists - pharmacology
/ Gene Expression Regulation - genetics
/ Light
/ Luminescent Proteins - genetics
/ Luminescent Proteins - metabolism
/ Mice
/ Motor Activity - radiation effects
/ Photic Stimulation - methods
/ Retina
/ Retinal Bipolar Cells - physiology
/ Retinal Bipolar Cells - radiation effects
/ Retinal Degeneration - pathology
/ Retinal Degeneration - physiopathology
/ Retinal Degeneration - therapy
/ Retinal Ganglion Cells - physiology
/ Vision, Ocular - radiation effects
/ Visual Pathways - drug effects
