rss
Br J Ophthalmol 2008;92:272-275 doi:10.1136/bjo.2007.126318
  • Original Article
    • Laboratory science

Long-term engraftment of systemically transplanted, gene-modified bone marrow-derived cells in the adult mouse retina

  1. C Boettcher1,
  2. E Ulbricht2,
  3. D Helmlinger3,
  4. A F Mack4,
  5. A Reichenbach2,
  6. P Wiedemann5,
  7. H-J Wagner4,
  8. M W Seeliger6,
  9. A Bringmann5,
  10. J Priller1
  1. 1
    Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany
  2. 2
    Paul Flechsig Institute of Brain Research, Faculty of Medicine, University of Leipzig, Leipzig, Germany
  3. 3
    Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France
  4. 4
    Institute of Anatomy, University of Tübingen, Tübingen, Germany
  5. 5
    Department of Ophthalmology and Eye Clinic, Faculty of Medicine, University of Leipzig, Leipzig, Germany
  6. 6
    Ocular Neurodegeneration Research Group, Institute for Ophthalmic Research, Department of Ophthalmology, University of Tübingen, Tübingen, Germany
  1. Dr J Priller, Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Schumannstr. 20/21, 10117 Berlin, Germany; josef.priller{at}charite.de
  • Accepted 31 October 2007

Abstract

Aims: To provide evidence for a novel route of gene administration to normal and diseased retinas, we performed systemic transplantation of genetically engineered bone marrow-derived cells (BMDCs) to wild-type mice and to mutant mice with retinal degeneration.

Methods: Lethally irradiated recipient mice—C57BL/6 (wild-type), SCA7 (spinocerebellar ataxia type 7) and FVB/N (rd1 mutant)—were transplanted intravenously with 5×106 BMDCs, which were transduced with a retroviral vector to express the enhanced green fluorescent protein (GFP). Chimeras were killed at 1, 3, 8, 11, 12 and 15 months (wild-type) or at 8 and 12 months (mutants) after transplantation. Eyes were enucleated, and the retinas were analysed using immunohistochemistry.

Results: In wild-type retinas, BMDCs preferentially engrafted in the inner and outer plexiform layers, the ganglion cell layer and the optic nerve. No BMDCs were found in the photoreceptor layer. BMDCs were more common in the degenerating retinas of the mutant mice. The majority of BMDCs in the retina were identified as microglia based on morphology and immunophenotype. Approximately 8–16% of all CD11b+ cells in the retina expressed GFP. None of the BMDCs expressed neuronal cell markers. GFP-expressing BMDCs were found to persist for more than 1 year after transplantation.

Conclusions: We demonstrate that gene-modified BMDCs show long-term engraftment and stable expression of GFP from a retrovirus in both wild-type and mutant mouse retinas. Thus, BMDCs may be used as vehicles for gene delivery to the retina.

Footnotes

  • Competing interests: None.

  • Funding: This work was supported by grants from the Deutsche Forschungsgemeinschaft (to JP, AR and MWS) and the Interdisziplinäres Zentrum für Klinische Forschung (IZKF) at the Faculty of Medicine, University of Leipzig (C35, Z10).

  • Ethics approval: All animal procedures were approved by the local authorities.

This Article

  1. Abstract
  2. Full text
  3. PDF

Responses

  1. Submit a response
  2. No responses published

Register for free content

The full back archive is now available for all BMJ Journals. Institutional subscribers may access the entire archive as part of their subscription. Personal subscribers will also have access to all content when logged in. Non-subscribers who register have free access to all articles published before 2006 right back to volume 1 issue 1. Register here to access the free archive of all BMJ Journals.

Don't forget to sign up for content alerts so you keep up to date with all the articles as they are published.