Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration

Nat Neurosci. 2008 Jun;11(6):667-75. doi: 10.1038/nn.2117. Epub 2008 Apr 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal
  • Disease Models, Animal
  • Electroporation / methods
  • 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
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Activity / physiology
  • Motor Activity / radiation effects
  • Patch-Clamp Techniques
  • Photic Stimulation / methods
  • Piperazines / pharmacology
  • Quinoxalines / pharmacology
  • Retinal Bipolar Cells / physiology*
  • Retinal Bipolar Cells / radiation effects
  • Retinal Degeneration* / pathology
  • Retinal Degeneration* / physiopathology
  • Retinal Degeneration* / therapy
  • Retinal Ganglion Cells / physiology
  • Rhodopsin / physiology*
  • Time Factors
  • Vision, Ocular / physiology*
  • Vision, Ocular / radiation effects
  • Visual Pathways / drug effects
  • Visual Pathways / physiology
  • Visual Pathways / radiation effects


  • Excitatory Amino Acid Antagonists
  • Luminescent Proteins
  • Piperazines
  • Quinoxalines
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Rhodopsin
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid