Journal
STEM CELL REPORTS
Volume 10, Issue 2, Pages 406-421Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2017.12.008
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Funding
- Medical Research Council UK [mr/j004553/1]
- Fight for Sight [1448/1449, 1351/2]
- European Research Council [ERC-2012-ADG_20120314]
- RP Fighting Blindness [GR576]
- Moorfields Eye Charity
- National Institute for Health Research (NIHR) Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital
- UCL Institute of Ophthalmology [BRC2-007]
- Macular Vision Research Foundation
- Child Health Research Appeal Trust
- NIHR Biomedical Research Centre for Pediatric Research at Great Ormond Street Hospital for Children
- UCL Institute of Child Health
- NIHR Great Ormond Street Hospital Biomedical Research Centre (GOSH BRC)
- GOSHCC
- Alcon Research Institute Young Investigator Award [UF120046]
- MRC [MR/L012758/1, MR/J004553/1, MR/M007871/1] Funding Source: UKRI
- Fight for Sight [1566/1567, 1448/49] Funding Source: researchfish
- Medical Research Council [MR/M007871/1, 1085159, MR/L012758/1, MR/J004553/1] Funding Source: researchfish
- National Institute for Health Research [NIHR-RP-011-003, NF-SI-0513-10074, NF-SI-0508-10130] Funding Source: researchfish
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Human vision relies heavily upon cone photoreceptors, and their loss results in permanent visual impairment. Transplantation of healthy photoreceptors can restore visual function in models of inherited blindness, a process previously understood to arise by donor cell integration within the host retina. However, we and others recently demonstrated that donor rod photoreceptors engage in material transfer with host photoreceptors, leading to the host cells acquiring proteins otherwise expressed only by donor cells. We sought to determine whether stem cell- and donor-derived cones undergo integration and/or material transfer. We find that material transfer accounts for a significant proportion of rescued cells following cone transplantation into non-degenerative hosts. Strikingly, however, substantial numbers of cones integrated into the Nrl(-/-) and Prph2(rd2/rd2), but not Nrl(-/-); RPE65(R91W/R91W), murine models of retinal degeneration. This confirms the occurrence of photoreceptor integration in certain models of retinal degeneration and demonstrates the importance of the host environment in determining transplantation outcome.
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