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E. L. West, R. A. Pearson, A. Barber, Y. Duran, J. C. Sowden, R. R. Ali; Immune Responses Affect the Survival of Integrated Photoreceptor Precursors Transplanted to the Adult Murine Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5242.
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© ARVO (1962-2015); The Authors (2016-present)
Photoreceptor transplantation is a novel strategy to repair the degenerate retina. We previously demonstrated that post-mitotic photoreceptor precursors can functionally integrate into the adult wild type and degenerating retina. However, these cells are lost over time. To determine the cause of this loss of transplanted cells, we sought to characterise their survival in non-degenerate retinas without the confounding factors of retinal disease.
GFP labelled progenitor cells from dissociated murine P3 retinas (H-2s2 x H-2b) were transplanted subretinally into partially matched adult recipient mice (H-2b) and photoreceptor integration was quantified 1 to 12 months later. We investigated the presence of immune cells at the site of injection and the effect of the immune suppressant cyclosporin A on the number of integrated photoreceptors at 1 and 4 months post transplantation.
In a minority of eyes an acute loss of integrated photoreceptors 1 month post injection correlated with the presence of macrophages at the injection site. Immune suppression did not affect this loss. In the majority of eyes, integrated photoreceptor cells were still present in the outer nuclear layer at 2 months post transplantation, however these cells were almost completely lost by 6 months. Macrophages and T cells were present throughout this period indicating a chronic immunological response. Immunosuppressive treatment following transplantation markedly increased the survival of integrated photoreceptors after 4 months.
Despite the high level of MHC compatibility between our donor cells and the host retina, long term loss of integrated photoreceptor cells after transplantation is associated with a chronic immune response in the host retina. These results suggest that development of MHC-matched or iPS-derived photoreceptor precursors may be required for long-term survival.
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