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F.K. Ghosh, K. Engelsberg, R.M. Petters; Long–Term Neuroretinal Full–Thickness Transplants in Severely Degenerated Rhodopsin Transgenic Pigs . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4162.
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Purpose: To explore transplantation of normal fetal neuroretina to eyes with severe retinitis pigmentosa and to establish graft development, long–term survival and effects on the host retina. Methods: Six Pro 347 Leu rhodopsin transgenic pigs, aged 6 months, in one eye received a 2x3 mm full–thickness neuroretinal sheet from a normal E49 pig fetus by means of vitrectomy and retinotomy. The first 3 animals received a graft within 4 hours from harvest of the donor eye, and the remaining three received a graft kept in culture for 24–28 hrs. After a survival time of 6 months, eye specimens were studied in the light microscope, and with immunohistochemistry directed against rhodopsin. Results: Grafts were placed flat in the subretinal space of the host eye in all cases without per– or post–operative complications. In hematoxylin and eosin stained specimens, laminated grafts with proper polarity, measuring 2.1–3.4 mm were found in 5 out of 6 eyes. All grafts displayed a well developed outer nuclear layer, and rhodopsin labeling confirmed the presence of rod photoreceptors with outer segments facing the host retinal pigment epithelium. All grafts also displayed an area of degeneration and rosettes facing the remaining host neuroretina, and no apparent integration could be seen between laminated parts of the host and graft. The host retina contained only scattered remaining rods in the part straddling the transplant, but in other areas, the number of rhodopsin labeled rods was distinctly higher compared with the corresponding unoperated eye in 3 out of 5 cases. In the remaining 2 cases, the number of rods was approximately the same in the operated and unoperated eye. The one eye with no visible graft, displayed fewer rhodopsin labeled cells than the corresponding unoperated eye. Conclusions:: Full–thickness neuroretina can safely be transplanted to the subretinal space of a host eye featuring a severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology including rod photoreceptors, and survive for at least 6 months. Short–term culturing of the donor tissue preoperatively does not seem to adversely affect graft survival. The presence of a well developed graft can in some cases rescue remaining host rod photoreceptor cells in the entire retina.
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