PT  - JOURNAL ARTICLE
AU  - C Boettcher
AU  - E Ulbricht
AU  - D Helmlinger
AU  - A F Mack
AU  - A Reichenbach
AU  - P Wiedemann
AU  - H-J Wagner
AU  - M W Seeliger
AU  - A Bringmann
AU  - J Priller
TI  - Long-term engraftment of systemically transplanted, gene-modified bone marrow-derived cells in the adult mouse retina
AID  - 10.1136/bjo.2007.126318
DP  - 2008 Feb 01
TA  - British Journal of Ophthalmology
PG  - 272--275
VI  - 92
IP  - 2
4099  - http://bjo.bmj.com/content/92/2/272.short
4100  - http://bjo.bmj.com/content/92/2/272.full
SO  - Br J Ophthalmol2008 Feb 01; 92
AB  - 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.