Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration

Neuron. 2006 Apr 6;50(1):23-33. doi: 10.1016/j.neuron.2006.02.026.

Abstract

The death of photoreceptor cells caused by retinal degenerative diseases often results in a complete loss of retinal responses to light. We explore the feasibility of converting inner retinal neurons to photosensitive cells as a possible strategy for imparting light sensitivity to retinas lacking rods and cones. Using delivery by an adeno-associated viral vector, here, we show that long-term expression of a microbial-type rhodopsin, channelrhodopsin-2 (ChR2), can be achieved in rodent inner retinal neurons in vivo. Furthermore, we demonstrate that expression of ChR2 in surviving inner retinal neurons of a mouse with photoreceptor degeneration can restore the ability of the retina to encode light signals and transmit the light signals to the visual cortex. Thus, expression of microbial-type channelrhodopsins, such as ChR2, in surviving inner retinal neurons is a potential strategy for the restoration of vision after rod and cone degeneration.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Disease Models, Animal
  • Dose-Response Relationship, Radiation
  • Evoked Potentials, Visual / genetics
  • Evoked Potentials, Visual / radiation effects
  • Gene Expression / physiology*
  • Gene Transfer Techniques
  • Genetic Therapy / methods
  • Green Fluorescent Proteins / metabolism
  • Membrane Potentials / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Neurons / physiology
  • Patch-Clamp Techniques / methods
  • Photic Stimulation / methods
  • Photoreceptor Cells, Vertebrate / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / genetics
  • Retina / cytology
  • Retinal Degeneration / genetics*
  • Retinal Degeneration / physiopathology*
  • Retinal Degeneration / therapy
  • Rhodopsin / physiology*
  • Visual Pathways / physiology

Substances

  • Green Fluorescent Proteins
  • Rhodopsin