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J.O. Rauer, F.K. Ghosh; Immunogenicity of Neuroretinal Xenografts in Hosts Without Immunosuppression . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5149.
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© ARVO (1962-2015); The Authors (2016-present)
To evaulate the fate and immunogenicity of neuroretinal full–thickness and fragmented xenografts in the subretinal space.
Adult mixed strain pigmented rabbits receiving no immunosuppression were used as hosts, and Sprague–Dowley rat neuroretina as donors. Using vitreoretinal surgical techniques, the rabbits received either a full thickness fetal day 19 graft (n=8), or a fragmented neonatal day 2 graft (n=4). The eyes were examined after 91 (full–thickness grafts) and 7 days (fragmented grafts) with hematoxin and eosin, and immunohistochemically with antibodies against major histocompatibility complex (MHC) class 1 and 2.
Full thickness grafts survived in 5/8 eyes and 4 of these showed a laminated morphology with all retinal layers present, except outer segments. No inflammation was seen in these 4 specimens. In the 5th specimen, a degenerated graft was found with breaks in the host RPE, inflammation in the choroid and a large amount of MHC–2 positive cells in the graft and choroid. In the remaining 3 eyes no graft was found. There was no inflammation in 2 eyes. In 1 eye, where the graft was found in the vitreous the postoperative day, there were large breaks in the RPE and inflammation in the choroid. In the eyes receiving fragmented grafts, degenerating grafts organized in rosettes were seen 4/4 eyes. Multiple RPE breaks and severe inflammation in the choroid were seen.
Immature full–thickness neuroretinal xenografts can survive in the subretinal space for at least 91 days in an adult host without immunosuppression. The grafts in the majority of cases survive for an extended time period, and develop into a laminated retina without signs of inflammation indicating a low degree of immunogenicity. Immature fragmented xenografts on the other hand, display a degenerated morphology already after 7 days with marked signs of rejection. We conclude that the integrity of xenogeneic neuroretinal donor tissue is of great importance for graft survival, and if such tissue is handled with care, it survives in the host subretinal space without immunosuppression.
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