Rescue of photoreceptor function by AAV-mediated gene transfer in a mouse model of inherited retinal degeneration

Gene Ther. 1997 Jul;4(7):683-90. doi: 10.1038/


Knowledge of the mutations leading to inherited retinal degenerations provides a foundation for the development of somatic gene therapy in which potentially corrective genes are transferred to the target photoreceptor cells. Towards this end, we have evaluated the efficacy of a recombinant adeno-associated virus (AAV) vector to deliver and express the correct form of the cGMP phosphodiesterase-beta (PDE-beta) gene in the retinas of rd mice, which suffer rapid retinal degeneration due to recessive mutation in the endogenous gene. A truncated murine opsin promoter was used to drive expression of the PDE-beta cDNA. Following intraocular injection of AAV. PDE-beta, increased retinal expression of immunoreactive PDE protein was observed, including within photoreceptor cell bodies. Compared with age-matched controls, treated eyes showed increased numbers of photoreceptors and a two-fold increase in sensitivity to light as measured by in vitro electroretinography. These findings provide evidence that rescue of functional photoreceptor neurons can be achieved by somatic gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dependovirus*
  • Disease Models, Animal
  • Electroretinography
  • Gene Transfer Techniques*
  • Genetic Vectors*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Photoreceptor Cells / pathology
  • Photoreceptor Cells / physiology*
  • Retinal Degeneration / genetics*
  • Retinal Degeneration / pathology
  • Retinal Degeneration / therapy