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Mandeep S Singh, Sher A Aslam, Isabel L Duncan, Alona O Cramer, Alun R Barnard, Robert E MacLaren; Cell fusion following photoreceptor transplantation into the non-degenerate retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3989.
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Photoreceptor transplantation could be a future treatment for retinal degenerations. In end-stage retinal degeneration, when no photoreceptor cells remain, the goal is to repopulate the retina with transplanted photoreceptors in order to restore vision. However, in certain forms of congenital stationary night blindness and Leber congenital amaurosis, there are vast numbers of intact host photoreceptors in the outer nuclear layer (ONL) despite visual dysfunction. Hence, in these conditions, photoreceptor transplantation into the well-formed host ONL could lead to fusion between donor and host cells that would result in the artefactual appearance of integrated cells. We aimed to investigate if transplanted photoreceptor precursors would fuse with coexisting photoreceptors in non-degenerate hosts.
Photoreceptor precursors were obtained from neonatal donor mice, in which rod and/or cone photoreceptors were fluorescent. Transplantation was performed into hosts with an intact ONL. Hosts were selected on the basis of differential fluorescent marker expression, in order to facilitate the accurate tracking of donor and host cells after the procedure. Histological analysis was conducted 2-3 weeks after transplantation.
ONL cells were identified in which the fluorescent markers of the donor and host photoreceptors were colocalised in the same cell. In addition, fluorescence was detected in cells in which they were not originally restricted, indicating transfer of fluorescent proteins between cells. The arrangement of fluorescent photoreceptor cell bodies in colour-concordant ONL columns suggested that fluorescence had been transferred to the host from donor cells located in the subretinal space, which were in intimate contact with the host outer segments.
Donor photoreceptors, when transplanted into a non-degenerate host retina, fuse with host photoreceptors in the ONL. This results in the transfer of proteins between the cells, including fluorescent markers. The appearance of well-integrated transplanted photoreceptors in non-degenerate hosts is the result of a fusion artefact. This phenomenon should be considered when designing clinical trials of stem cell transplantation in the future.
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