title: Donor and host photoreceptors engage in material transfer following transplantation of post-mitotic photoreceptor precursors.
abstract: Photoreceptor replacement by transplantation is proposed as a treatment for blindness. Transplantation of healthy photoreceptor precursor cells into diseased murine eyes leads to the presence of functional photoreceptors within host retinae that express an array of donor-specific proteins. The resulting improvement in visual function was understood to be due to donor cells integrating within host retinae. Here, however, we show that while integration occurs the majority of donor-reporter-labelled cells in the host arises as a result of material transfer between donor and host photoreceptors. Material transfer does not involve permanent donor-host nuclear or cell-cell fusion, or the uptake of free protein or nucleic acid from the extracellular environment. Instead, RNA and/or protein are exchanged between donor and host cells in vivo. These data require a re-evaluation of the mechanisms underlying rescue by photoreceptor transplantation and raise the possibility of material transfer as a strategy for the treatment of retinal disorders.
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Pearson
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez-Cordero
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: E L
authors.initials: EL
authors.lastname: West
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Ribeiro
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: N
authors.initials: N
authors.lastname: Aghaizu
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: D
authors.initials: D
authors.lastname: Goh
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: R D
authors.initials: RD
authors.lastname: Sampson
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: A
authors.initials: A
authors.lastname: Georgiadis
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: P V
authors.initials: PV
authors.lastname: Waldron
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Duran
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: A
authors.initials: A
authors.lastname: Naeem
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: M
authors.initials: M
authors.lastname: Kloc
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: E
authors.initials: E
authors.lastname: Cristante
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: K
authors.initials: K
authors.lastname: Kruczek
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: K
authors.initials: K
authors.lastname: Warre-Cornish
authors.affiliation: Stem Cells and Regenerative Medicine Section, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Sowden
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Smith
authors.affiliation: Department of Genetics, University College London Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.|NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, City Road, London EC1V 2PD, UK.
authors.forename: R R
authors.initials: RR
authors.lastname: Ali
mesh_terms: D000818:Animals; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D020419:Photoreceptor Cells, Vertebrate / Q000637:transplantation*; D012313:RNA / Q000378:metabolism; D012160:Retina / Q000637:transplantation*; D012162:Retinal Degeneration / Q000378:metabolism; D012164:Retinal Diseases / Q000628:therapy*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism; D033581:Stem Cell Transplantation; D014019:Tissue Donors
chemical_list: D049452:Green Fluorescent Proteins; D012313:RNA