Document Detail

Use of topical FK506 in a corneal graft rejection model in Lewis rats.
MedLine Citation:
PMID:  9112986     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To evaluate the immunosuppressive effect of topical FK506 on allograft corneal rejection in rats. METHODS: Lewis rats were used as recipients and Fisher rats as corneal graft donors. In Experiment 1, all rats received intraperitoneally FK506 (0.3 mg/kg per day) for 7 days to ensure equal baseline parameters. The rats then were assigned randomly to treatment with topical 0.3% FK506 or vehicle alone. In another set of experiments, rats were treated only with topical treatment. The grafts were inspected by clinical evaluation. Corneas obtained at the time of maximum rejection were used for histology and immunohistochemistry. RESULTS: The selected combination of rat strains caused 100% graft rejection in untreated animals within 2 weeks after the penetrating keratoplasty. In the treated animals, rejection was delayed until the end of topical therapy. One third of corneal grafts remained clear until day 30. Histologic and immunohistochemical studies confirmed the clinical evaluations. Untreated rat corneas had a large number of infiltrating helper-inducer T cells, macrophages, interleukin-2 receptor-expressing cells, and Ia-antigen-expressing cells. At the same timepoint, topically treated corneas showed a limited inflammatory response characterized by a 2/3 reduction in the number of infiltrating helper and cytotoxic cells, and a five-fold decrease in the expression of class I and class II major histocompatibility antigens. CONCLUSIONS: Topical FK506 treatment is an effective way of preventing corneal graft rejection in the Lewis rat corneal graft model. It shows promise as a drug to prevent corneal graft rejection in humans.
N Hikita; J S Lopez; C C Chan; M Mochizuki; R B Nussenblatt; M D de Smet
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  38     ISSN:  0146-0404     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-05-02     Completed Date:  1997-05-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  901-9     Citation Subset:  IM    
Department of Ophthalmology, Kurume University School of Medicine, Japan.
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MeSH Terms
Administration, Topical
Cornea / drug effects*,  immunology,  metabolism,  pathology
Disease Models, Animal*
Graft Rejection / drug therapy*,  immunology,  pathology
Histocompatibility Antigens Class II / metabolism
Immunosuppressive Agents / administration & dosage,  therapeutic use*
Keratoplasty, Penetrating* / immunology,  pathology
Macrophages / pathology
Ophthalmic Solutions
Rats, Inbred F344
Rats, Inbred Lew
Receptors, Interleukin-2 / metabolism
T-Lymphocytes, Cytotoxic / pathology
T-Lymphocytes, Helper-Inducer / pathology
Tacrolimus / administration & dosage,  therapeutic use*
Transplantation, Homologous
Reg. No./Substance:
0/Histocompatibility Antigens Class II; 0/Immunosuppressive Agents; 0/Ophthalmic Solutions; 0/Receptors, Interleukin-2; 109581-93-3/Tacrolimus

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