title: Phagocytosis of photoreceptor outer segments by transplanted human neural stem cells as a neuroprotective mechanism in retinal degeneration.
abstract: OBJECTIVE
  Transplantation of human central nervous system stem cells (HuCNS-SC) into the subretinal space of Royal College of Surgeons (RCS) rats preserves photoreceptors and visual function. To explore possible mechanism(s) of action underlying this neuroprotective effect, we performed a detailed morphologic and ultrastructure analysis of HuCNS-SC transplanted retinas.
  
  
  METHODS
  The HuCNS-SC were transplanted into the subretinal space of RCS rats. Histologic examination of the transplanted retinas was performed by light and electron microscopy. Areas of the retina adjacent to HuCNS-SC graft (treated regions) were analyzed and compared to control sections obtained from the same retina, but distant from the transplant site (untreated regions).
  
  
  RESULTS
  The HuCNS-SC were detected as a layer of STEM 121 immunopositive cells in the subretinal space. In treated regions, preserved photoreceptor nuclei, as well as inner and outer segments were identified readily. In contrast, classic signs of degeneration were observed in the untreated regions. Interestingly, detailed ultrastructure analysis revealed a striking preservation of the photoreceptor-bipolar-horizontal cell synaptic contacts in the outer plexiform layer (OPL) of treated areas, in stark contrast with untreated areas. Finally, the presence of phagosomes and vesicles exhibiting the lamellar structure of outer segments also was detected within the cytosol of HuCNS-SC, indicating that these cells have phagocytic capacity in vivo.
  
  
  CONCLUSIONS
  This study reveals the novel finding that preservation of specialized synaptic contacts between photoreceptors and second order neurons, as well as phagocytosis of photoreceptor outer segments, are potential mechanism(s) of HuCNS-SC transplantation, mediating functional rescue in retinal degeneration.
authors.affiliation: Department of Physiology, Genetics and Microbiology, University of Alicante, San Vicente del Raspeig, Spain.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Cuenca
authors.forename: Laura
authors.initials: L
authors.lastname: Fernández-Sánchez
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: McGill
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.forename: Shaomei
authors.initials: S
authors.lastname: Wang
authors.forename: Raymond
authors.initials: R
authors.lastname: Lund
authors.forename: Stephen
authors.initials: S
authors.lastname: Huhn
authors.forename: Alexandra
authors.initials: A
authors.lastname: Capela
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D046529:Microscopy, Electron, Transmission; D058953:Neural Stem Cells / Q000637:transplantation* / Q000648:ultrastructure; D010587:Phagocytosis / Q000502:physiology*; D051381:Rats; D012162:Retinal Degeneration / Q000473:pathology / Q000601:surgery*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000502:physiology* / Q000648:ultrastructure; D033581:Stem Cell Transplantation / Q000379:methods*
keywords: electron microscopy; phagocytosis; retinal degeneration; synaptic contacts; therapy; transplant