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

C Boettcher, E Ulbricht, D Helmlinger, A F Mack, A Reichenbach, P Wiedemann, H-J Wagner, M W Seeliger, A Bringmann, J Priller

Research output: Contribution to journalArticlepeer-review

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 5x106 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.

Original languageEnglish
Pages (from-to)272-5
Number of pages4
JournalBritish Journal of Ophthalmology
Volume92
Issue number2
DOIs
Publication statusPublished - Feb 2008

Keywords

  • Animals
  • Bone Marrow Transplantation
  • Gene Transfer Techniques
  • Genetic Engineering
  • Graft Survival
  • Green Fluorescent Proteins
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Retina
  • Retinal Degeneration
  • Transduction, Genetic
  • Journal Article
  • Research Support, Non-U.S. Gov't

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