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K. Narfstrom, K. Warfvinge, P. H. Schwartz, M. J. Young, G. Tullis, S. Eftekhari, C. Hamm, D. Hainsworth, H. Klassen; Integration of Feline Neural Precursor Cells After Subretinal Transplantation Into Abyssinian Cats Affected With Hereditary Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4064.
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The purpose was to determine whether neural progenitor cells survive subretinal transplantation, show evidence of integration, and exert positive effects on the feline host degenerative retina.
45-day old feline fetal brains were obtained, neural precursors cultured and labeled by EGFP through transfection with the lentiviral vector FUGW. The recipients were six 2-5 year-old Abyssinian cats affected with hereditary rod cone degeneration. Aseptic vitreo-retinal surgery was performed as previously described, and 75 microliters of pre-labeled donor cells (750,000) were injected subretinally into one eye. The fellow eye was not treated. Post-op. examination included ophthalmoscopy, bilateral full-field electroretinography (ERG) and immunohistochemistry for Vimentin and GFAP. Histological sections were evaluated using fluorescence and confocal microscopy. Five cats were euthanized at 2 (n=2) and 4 weeks (n=3) post-op. and one was used for long-term follow-up.
No adverse effects were noted. ERGs showed up to 20% reduced ERG b-wave amplitudes 4 weeks post-op., but long-term amplitudes increased in the transplanted eye 10 months post-op. compared to the untreated eye. Morphology has not yet been evaluated, but in the others showed GFP+ cells with resemblance to RPE, Mueller, and bipolar cells.
Feline neural progenitor cells survive up to 4 weeks subretinally, migrate in the dystrophic feline retina and develop into cells with features characteristic of the local microenvironment. ERG responses were reduced post-op. but one animal studied long-term shows evidence suggestive of functional benefit.
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