Stable and efficient gene transfer into the mutant retinal pigment epithelial cells of the Mitf(vit) mouse using a lentiviral vector

Curr Eye Res. 1999 Feb;18(2):135-42. doi: 10.1076/ceyr.18.2.135.5376.

Abstract

Purpose: The purpose of the present study was to test whether a lentiviral vector encoding the marker lacZ gene under the control of the human CMV promoter would stably infect a significant number of RPE cells in the vitiligo mouse. This mouse harbors a mutation in the microphthalmia gene in RPE cells that leads to slow progressive photoreceptor cell degeneration.

Methods: Concentrated lentiviral vector HR'CMVlacZ was injected intravitreally into newborn vitiligo mice. Mice were sacrificed at various time points up to two months post-injection and eyes were processed histochemically to detect lacZ expression.

Results: The lentiviral vector infected predominantly the RPE and resulted in lacZ expression in numerous RPE cells at all times analyzed.

Conclusions: LacZ expression in vitiligo RPE cells appeared to be stable for a period of at least two months. These results raise the possibility of using a similar lentiviral vector for introduction of a correct copy of the microphthalmia cDNA into the RPE that may ultimately rescue photoreceptor cells in this mutant mouse.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • DNA-Binding Proteins / genetics*
  • Gene Transfer Techniques*
  • Genetic Vectors*
  • Lac Operon / genetics
  • Lentivirus / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Microphthalmia-Associated Transcription Factor
  • Pigment Epithelium of Eye / pathology
  • Pigment Epithelium of Eye / virology*
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • Transcription Factors