title: Bimodal in vivo imaging provides early assessment of stem-cell-based photoreceptor engraftment.
abstract: OBJECTIVE
  Subretinal transplantation of stem-cell-derived photoreceptor precursor cells (PPCs) is a promising and innovative approach to treating a range of blinding diseases. However, common barriers to efficient preclinical transplantation comes in the form of suboptimal graft architecture, limited graft survival, and immune-rejection, each of which cannot be assessed using conventional in vivo imaging (i.e., rodent ophthalmoscopy). With the majority of PPCs reported to die within the first few weeks after transplantation, understanding the mechanisms of graft failure, and ultimately devising preventative methods, currently relies on lengthy end point histology. To address these limitations, we hypothesized that combining two imaging modalities, optical coherence tomography (OCT) and fluorescence confocal scanning laser ophthalmoscopy (fcSLO), could provide a more rapid and comprehensive view of PPC engraftment.
  
  
  METHODS
  Human ESC-derived PPCs were transplanted into 15 retinal dystrophic rats that underwent bimodal imaging at 0, 8, and 15 days posttransplant.
  
  
  RESULTS
  Bimodal imaging provided serial detection of graft: placement, architecture, and survival; each undetectable under ophthalmoscopy. Bimodal imaging determined graft placement to be either: subretinal (n=7), choroidal (n=4), or vitreal (n=4) indicating neural retinal perforation. Graft architecture was highly variable at the time of transplantation, with notable redistribution over time, while complete, or near complete, graft loss was observed in the majority of recipients after day 8. Of particular importance was detection of vitreal aggregates overlying the graft-possibly an indicator of host-site inflammation and rejection.
  
  
  CONCLUSIONS
  Early real-time feedback of engraftment has the potential to greatly increase efficiency of preclinical trials in cell-based retinal therapeutics.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: C R J
authors.initials: CR
authors.lastname: Laver
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: A L
authors.initials: AL
authors.lastname: Metcalfe
authors.affiliation: Department of Molecular Biology and Biochemistry, Faculty of Science, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Szczygiel
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Yanai
authors.affiliation: School of Engineering Science, Faculty of Applied Science, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: M V
authors.initials: MV
authors.lastname: Sarunic
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Gregory-Evans
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D006085:Graft Survival / Q000502:physiology*; D000066449:Human Embryonic Stem Cells / Q000637:transplantation*; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D009887:Ophthalmoscopy / Q000379:methods; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000637:transplantation*; D045663:Quantum Dots; D051381:Rats; D012162:Retinal Degeneration / Q000601:surgery*; D041623:Tomography, Optical Coherence / Q000379:methods; D014183:Transplantation, Heterologous