Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, Levels 5-6 West Wing, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
UK Ministry of Defence Army Medical Services, London SW1A 2HB, UK.
Nat Commun. 2016 Nov 30;7:13537. doi: 10.1038/ncomms13537.
Photoreceptor transplantation is a potential future treatment for blindness caused by retinal degeneration. Photoreceptor transplantation restores visual responses in end-stage retinal degeneration, but has also been assessed in non-degenerate retinas. In the latter scenario, subretinal transplantation places donor cells beneath an intact host outer nuclear layer (ONL) containing host photoreceptors. Here we show that host cells are labelled with the donor marker through cytoplasmic transfer-94±4.1% of apparently well-integrated donor cells containing both donor and host markers. We detect the occurrence of Cre-Lox recombination between donor and host photoreceptors, and we confirm the findings through FISH analysis of X and Y chromosomes in sex-discordant transplants. We do not find evidence of nuclear fusion of donor and host cells. The artefactual appearance of integrated donor cells in host retinas following transplantation is most commonly due to material transfer from donor cells. Understanding this novel mechanism may provide alternate therapeutic strategies at earlier stages of retinal degeneration.
光感受器移植是治疗视网膜变性引起的失明的一种有潜力的未来疗法。光感受器移植恢复了晚期视网膜变性的视觉反应，但也在非变性视网膜中进行了评估。在后一种情况下，视网膜下移植将供体细胞置于完整的宿主外核层（ONL）下方，其中包含宿主光感受器。在这里，我们发现宿主细胞通过细胞质转移被供体标记-94±4.1％的明显整合良好的供体细胞包含供体和宿主标记物。我们检测到供体和宿主光感受器之间发生 Cre-Lox 重组，并且我们通过 X 和 Y 染色体在性别不同的移植中的 FISH 分析证实了这一发现。我们没有发现供体和宿主细胞核融合的证据。移植后，宿主视网膜中整合的供体细胞的人为外观通常是由于供体细胞的物质转移所致。了解这种新的机制可能为视网膜变性的早期阶段提供替代的治疗策略。
