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T.M. Holmes, B. Lu, R.D. Lund; Human RPE Cell Transplants Retard the Secondary Vascular Events of RCS Rat Retinal Degeneration . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4972.
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Purpose:To determine the effects of RPE transplantation on the secondary vascular events of the RCS dystrophy before, during and after rod photoreceptor loss. Methods:Human ARP19 cells in suspension were transplanted into the dorsal subretinal space of dystrophic RCS rats at 21 d and 3 months of age. The animals were sacrificed at 2 months, 4 months and 6 months of age, the retinas removed, flat mounted and the vasculature stained using the NADPH diaphorase method. Results:Vascular abnormalities can be seen on flat mounted unoperated RCS retinae starting at 2-3 months of age in the ventral retina, and progressing into the rest of the retina and increasing in complexity with age. Transplants given at 21days and flat mounted at 2 months clearly exhibit pigmented cells clustered along veins (but not arteries) around the graft site: these cells are not associated with any disturbance of the vascular network. Three months after transplantation, no pigmented cells can be observed and the entire retina is practically clear of secondary vascular events in contrast to untreated retinae. At 5 months after transplantation the retinae are identical to untreated controls. Transplants given at 3 months and studied at 4 months exhibit secondary vascular events in addition to pigmented cells immediately around the transplant site that are not associated with vascular abnormalities. Conclusions:Transplantation of ARP19 cells into dystrophic RCS rats slows down the progression of secondary vascular events across the entire retina but does not stop them from forming completely. Transplantation of cells after photoreceptor loss has no noticeable effect on the secondary events. Transplant delivery must be given before photoreceptor loss to be effective and modification of transplanted cells may be required to give a longer lasting/permanent effect.
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