Document Detail

Macrophages play a role in the early phase of corneal allograft rejection in rats.
MedLine Citation:
PMID:  15201661     Owner:  NLM     Status:  MEDLINE    
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.
Tanja P A M Slegers; Lidy Broersma; Nico van Rooijen; Johanna M M Hooymans; Gabriel van Rij; Ruth van der Gaag
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  77     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-06-17     Completed Date:  2004-07-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1641-6     Citation Subset:  IM    
Department of Ophthalmology, University Hospital Groningen, Groningen, The Netherlands.
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MeSH Terms
Clodronic Acid / administration & dosage
Cornea / pathology
Corneal Transplantation*
Drug Administration Schedule
Graft Rejection / physiopathology*,  prevention & control
Graft Survival
Macrophages* / pathology
Rats, Inbred Strains
Transplantation, Homologous
Reg. No./Substance:
0/Liposomes; 10596-23-3/Clodronic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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