title: Host-derived endothelial regeneration of corneal transplants in a rat keratoplasty model.
abstract: BACKGROUND
  It has been observed that formerly rejected opaque corneal transplants can regain clarity in the rat. We hypothesized that graft endothelium is regenerated by the host. Therefore, we used green fluorescent protein (GFP) transgenic rats to assess the origin of cells following keratoplasty.
  
  
  METHODS
  Allogeneic corneal transplantations were carried out between Fischer strain rats as graft donors and GFP-transgenic Lewis rats as recipients. In a second group, syngeneic transplantations were performed between GFP-negative Lewis donors and GFP-positive Lewis recipients, where endothelial-cell-free grafts after mechanical endothelial debridement were used. All grafts were followed up clinically for signs of opacity and rejection. After 6 weeks, corneal flatmounts counterstained with DAPI were analyzed by confocal microscopy.
  
  
  RESULTS
  Syngeneic transplantation of endothelial-cell-free grafts led to medium opacity levels without rejection and to subsequent clearing. All grafts showed a population of GFP-positive, host-derived endothelial cells on the graft after 6 weeks. In the allogeneic transplantation group, all grafts but one were rejected after a median of 17 days. While the graft that was not rejected maintained the GFP-negative transplant endothelium, all formerly rejected grafts showed GFP-positive endothelium on the transplant after 6 weeks, accompanied by clinical clearing of the graft.
  
  
  CONCLUSIONS
  GPF positivity shows that in both a syngeneic and an allogeneic setting, the host-derived corneal endothelium can compensate for the endothelial cell loss of the graft. Following rejection, the grafts are repopulated by host-derived endothelial cells in the rat. This finding demonstrates a high regenerative capacity of the peripheral corneal endothelium in the rat, which should be considered whenever interpreting rat keratoplasty results.
authors.affiliation: University Eye Hospital Freiburg, Freiburg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Bredow
authors.forename: Johannes
authors.initials: J
authors.lastname: Schwartzkopff
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinhard
mesh_terms: D064591:Allografts; D000818:Animals; D019070:Cell Lineage / Q000502:physiology*; D003318:Corneal Opacity / Q000473:pathology; D016039:Corneal Transplantation; D004195:Disease Models, Animal; D004728:Endothelium, Corneal / Q000166:cytology / Q000502:physiology*; D006084:Graft Rejection / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D049408:Luminescent Agents / Q000378:metabolism; D018613:Microscopy, Confocal; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D055647:Rats, Transgenic; D012038:Regeneration / Q000502:physiology*; D014019:Tissue Donors; D066027:Transplant Recipients; D014185:Transplantation, Isogeneic
chemical_list: D049408:Luminescent Agents; D049452:Green Fluorescent Proteins