title: Macrophages play a role in the early phase of corneal allograft rejection in rats.
abstract: BACKGROUND
  Rat corneal allograft rejection is delayed by repeated local injection of liposomes filled with clodronate (dichloromethylene diphosphonate), which selectively deplete macrophages. Various administration schedules of liposomes were tested to determine the optimum schedule for prevention of graft rejection. Cell subpopulations in the anterior segment of the eye were studied at different time points after transplantation to assess the kinetics of the immune response.
  
  
  METHODS
  AO rats were grafted orthotopically with corneal buttons from PVG rats. Postoperatively, rats remained untreated or received clodronate liposomes subconjunctivally. Clodronate liposomes were injected five times on postoperative days (PODs) 0, 2, 4, 6, and 8; or once, on POD 0 or 6; or twice on PODs 0 and 2 or PODs 0 and 6. Grafts were examined for signs of rejection clinically and immunohistologically.
  
  
  RESULTS
  All untreated rats rejected their grafts as did all five rats that received clodronate liposomes once on POD 6. In all the other administration schedules tested, graft survival was prolonged compared with the untreated control group (P <0.01). Injections of clodronate liposomes on PODs 0 and 2 proved to be the most effective treatment. Histologically reduced influx of virtually all cell types tested was found in this group.
  
  
  CONCLUSIONS
  To prevent or delay graft rejection, it is necessary to administer clodronate liposomes in the early phase after corneal transplantation. These results suggest a role for macrophages in the afferent phase of corneal graft rejection.
authors.affiliation: Department of Ophthalmology, University Hospital Groningen, Groningen, The Netherlands. t.slegers@ohk.azg.nl
authors.forename: Tanja P A M
authors.initials: TP
authors.lastname: Slegers
authors.forename: Lidy
authors.initials: L
authors.lastname: Broersma
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Johanna M M
authors.initials: JM
authors.lastname: Hooymans
authors.forename: Gabriel
authors.initials: G
authors.lastname: van Rij
authors.forename: Ruth
authors.initials: R
authors.lastname: van der Gaag
mesh_terms: D000818:Animals; D004002:Clodronic Acid / Q000008:administration & dosage; D003228:Conjunctiva; D003315:Cornea / Q000473:pathology; D016039:Corneal Transplantation; D004334:Drug Administration Schedule; D006084:Graft Rejection / Q000503:physiopathology* / Q000517:prevention & control; D006085:Graft Survival; D007267:Injections; D008081:Liposomes; D008264:Macrophages / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014184:Transplantation, Homologous
chemical_list: D008081:Liposomes; D004002:Clodronic Acid