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

Mandeep Singh, Jasmin Balmer, Alun R. Barnard, Sher A. Aslam, Daniela Moralli, Catherine M. Green, Alona Barnea-Cramer, Isabel Duncan, Robert E. MacLaren

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number13537
JournalNature Communications
Volume7
DOIs
StatePublished - Nov 30 2016
Externally publishedYes

Fingerprint

photoreceptors
Transplants
Protein Precursors
Chromosomes
transplantation
Fusion reactions
fusion
proteins
Retinal Degeneration
degeneration
Transplantation
cells
Proteins
retina
markers
Retina
Nuclear Fusion
blindness
Y Chromosome
chromosomes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Transplanted photoreceptor precursors transfer proteins to host photoreceptors by a mechanism of cytoplasmic fusion. / Singh, Mandeep; Balmer, Jasmin; Barnard, Alun R.; Aslam, Sher A.; Moralli, Daniela; Green, Catherine M.; Barnea-Cramer, Alona; Duncan, Isabel; MacLaren, Robert E.

In: Nature Communications, Vol. 7, 13537, 30.11.2016.

Research output: Contribution to journalArticle

Singh, M, Balmer, J, Barnard, AR, Aslam, SA, Moralli, D, Green, CM, Barnea-Cramer, A, Duncan, I & MacLaren, RE 2016, 'Transplanted photoreceptor precursors transfer proteins to host photoreceptors by a mechanism of cytoplasmic fusion', Nature Communications, vol. 7, 13537. https://doi.org/10.1038/ncomms13537
Singh, Mandeep ; Balmer, Jasmin ; Barnard, Alun R. ; Aslam, Sher A. ; Moralli, Daniela ; Green, Catherine M. ; Barnea-Cramer, Alona ; Duncan, Isabel ; MacLaren, Robert E. / Transplanted photoreceptor precursors transfer proteins to host photoreceptors by a mechanism of cytoplasmic fusion. In: Nature Communications. 2016 ; Vol. 7.
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