4.6 Article

Transplanted Donor- or Stem Cell-Derived Cone Photoreceptors Can Both Integrate and Undergo Material Transfer in an Environment-Dependent Manner

Journal

STEM CELL REPORTS
Volume 10, Issue 2, Pages 406-421

Publisher

CELL PRESS
DOI: 10.1016/j.stemcr.2017.12.008

Keywords

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Funding

  1. Medical Research Council UK [mr/j004553/1]
  2. Fight for Sight [1448/1449, 1351/2]
  3. European Research Council [ERC-2012-ADG_20120314]
  4. RP Fighting Blindness [GR576]
  5. Moorfields Eye Charity
  6. National Institute for Health Research (NIHR) Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital
  7. UCL Institute of Ophthalmology [BRC2-007]
  8. Macular Vision Research Foundation
  9. Child Health Research Appeal Trust
  10. NIHR Biomedical Research Centre for Pediatric Research at Great Ormond Street Hospital for Children
  11. UCL Institute of Child Health
  12. NIHR Great Ormond Street Hospital Biomedical Research Centre (GOSH BRC)
  13. GOSHCC
  14. Alcon Research Institute Young Investigator Award [UF120046]
  15. MRC [MR/L012758/1, MR/J004553/1, MR/M007871/1] Funding Source: UKRI
  16. Fight for Sight [1566/1567, 1448/49] Funding Source: researchfish
  17. Medical Research Council [MR/M007871/1, 1085159, MR/L012758/1, MR/J004553/1] Funding Source: researchfish
  18. 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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