Retinal remodeling in the Tg P347L rabbit, a large-eye model of retinal degeneration

J Comp Neurol. 2011 Oct 1;519(14):2713-33. doi: 10.1002/cne.22703.

Abstract

Retinitis pigmentosa (RP) is an inherited blinding disease characterized by progressive loss of retinal photoreceptors. There are numerous rodent models of retinal degeneration, but most are poor platforms for interventions that will translate into clinical practice. The rabbit possesses a number of desirable qualities for a model of retinal disease including a large eye and an existing and substantial knowledge base in retinal circuitry, anatomy, and ophthalmology. We have analyzed degeneration, remodeling, and reprogramming in a rabbit model of retinal degeneration, expressing a rhodopsin proline 347 to leucine transgene in a TgP347L rabbit as a powerful model to study the pathophysiology and treatment of retinal degeneration. We show that disease progression in the TgP347L rabbit closely tracks human cone-sparing RP, including the cone-associated preservation of bipolar cell signaling and triggering of reprogramming. The relatively fast disease progression makes the TgP347L rabbit an excellent model for gene therapy, cell biological intervention, progenitor cell transplantation, surgical interventions, and bionic prosthetic studies.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Animals, Genetically Modified
  • Disease Models, Animal
  • Disease Progression
  • Electroretinography
  • Glutamic Acid / metabolism
  • Glutamine / metabolism
  • Glutathione / metabolism
  • Glycine / metabolism
  • Humans
  • Male
  • Opsins / metabolism
  • Rabbits
  • Retina / pathology
  • Retina / physiology*
  • Retina / physiopathology*
  • Retina / ultrastructure
  • Retinal Degeneration / pathology
  • Retinal Degeneration / physiopathology*
  • Retinitis Pigmentosa / pathology
  • Retinitis Pigmentosa / physiopathology*
  • Taurine / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Opsins
  • Glutamine
  • Taurine
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Glutathione
  • Glycine