Transplanted photoreceptor precursors transfer proteins to host photoreceptors by a mechanism of cytoplasmic fusion

被引：174

作者：

Singh, Mandeep S. ^{[1
]}

Balmer, Jasmin ^{[1
]}

Barnard, Alun R. ^{[1
]}

Aslam, Sher A. ^{[1
,2
]}

Moralli, Daniela ^{[3
]}

Green, Catherine M. ^{[3
]}

Barnea-Cramer, Alona ^{[1
]}

Duncan, Isabel ^{[1
]}

MacLaren, Robert E. ^{[1
,2
,4
]}

机构：

[1] Univ Oxford, John Radcliffe Hosp, Dept Clin Neurosci, Nuffield Lab Ophthalmol, Levels 5-6 West Wing,Headley Way, Oxford OX3 9DU, England

[2] UK Minist Def Army Med Serv, London SW1A 2HB, England

[3] Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England

[4] Moorfields Eye Hosp NHS Fdn Trust, 162 City Rd, London EC1V 2PD, England

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

RETINAL DEGENERATION; VISUAL FUNCTION; CELLS; MOUSE; MICE; REGENERATION; RESTORATION; EXPRESSION; INTEGRATE; MATURE;

D O I：

10.1038/ncomms13537

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：5

共 22 条

[1] Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors [J].