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A.B. Blixt, U. Englund, C. Lundberg, K. Warfvinge; Long-Distance Migration of Neural Precursor Cells Transplanted to Adult Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):484.
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Purpose: To demonstrate the mode of migration of precursor cells on whole mounted retina after transplantation to the subretinal space. Methods: The precursor cell line, RN33B, derived from the raphe nuclei was grafted via a trans-scleral route to the subretinal space of healthy adult rats. The cell line carries the marker genes for ß-galactosidase (ß-gal) and green fluorescent protein (GFP). 200.000 cells were injected unilaterally in the superonasal quadrant between ora serrata and the equator. All recipients were immunosuppressed daily with cyclosporine A. Two months post-transplantation the rats were sacrificed and the sensory retinas were whole mounted. A semi-automatized computer system was used to estimate the distribution area of the grafted cells throughout the retina. Results: A significant number of transplanted cells were found distant from the injection site. The migrated RN33B cells were distributed over almost the entire retina. The morphologies of the transplanted cells were bipolar to multipolar with branched processes. A large fraction of the grafted cells remained at or close to the implantation site. Occasionally chains of migrating precursor cells were found at the injection site, seemingly climbing along each other. These tubules resembled the chain migration tubules found in the rostral migratory stream (Alvarez-Buylla and García-Verdugo, J Neurosci 2002:22:629). Conclusions: Two months post-transplantation it was established that the RN33B cell line grafted subretinally migrated throughout almost the entire retina. In addition a fraction of the precursor cells transplanted to adult retina migrated in a chain-like manner. The extensive migratory capacity of the precursor cells could be useful in combination with ex vivo gene transfer to treat generalized retinal degeneration.
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