Evaluation of a topical cyclosporine A prodrug on corneal graft rejection in rats.

Details

Serval ID
serval:BIB_7E09A79A50C9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Evaluation of a topical cyclosporine A prodrug on corneal graft rejection in rats.
Journal
Molecular Vision
Author(s)
Bourges J.L., Lallemand F., Agla E., Besseghir K., Dumont J.M., BenEzra D., Gurny R., Behar-Cohen F.
ISSN
1090-0535 (Electronic)
ISSN-L
1090-0535
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
12
Pages
1461-1466
Language
english
Notes
Publication types: Journal ArticlePublication Status: epublish
Abstract
PURPOSE: To assess the efficacy of a topical cyclosporine A (CsA), water-soluble prodrug, for promoting the survival of allogenic rat corneal grafts after penetrating keratoplasty (PKP).
METHODS: Corneas of Brown-Norway rats (donors) were transplanted to Lewis rats (recipients). Transplanted rats were divided in three treatment groups: group I (PBS) and group II (0.26% Debio088) received drops five times per day. Group III received a daily intramuscular CsA injection (10 mg/kg/day). Blood CsA concentrations were measured on days 2 and 14. On day 4, 10, 13 after PKP, grafts were scored for corneal transparency, edema and extent of neovascularization. An opacity score of greater than or equal to 3 was considered as a nonreversible graft rejection process. On day 14, the experimental eyes were processed for histology.
RESULTS: On day 13, 12 of the 18 corneal transplants (67%) in group I showed irreversible graft rejection. Three of 18 transplants (19%) in group II and 5 of 16 transplants (28%) in group III showed irreversible graft rejection (p=0.013/p=0.019, OR=0.14/0.06 versus vehicle). Each mean clinical score for edema, opacity, and neovessels in group II were significantly lower than those of the grafts in group I (respectively p=0.010, p=0.013, p=0.024) and III except for neovessels (respectively p=0.002, p=0.001, p=0.057). Histology confirmed the clinical results. The mean CsA blood levels for groups II and III were, respectively 54+/-141 mug/l and 755+/-319 mug/l on day 2 and 14+/-34 mug/l and 1318+/-463 mug/l on day 14.
CONCLUSIONS: Debio088 CsA prodrug drops given five times daily are as effective as intramuscular injection of 10 mg/kg/day for the prevention of acute corneal graft rejection in rats.
Keywords
Administration, Topical, Animals, Corneal Edema/etiology, Corneal Edema/pathology, Corneal Opacity/etiology, Corneal Opacity/pathology, Cyclosporine/administration & dosage, Cyclosporine/adverse effects, Cyclosporins/administration & dosage, Cyclosporins/adverse effects, Drug Administration Schedule, Drug Evaluation, Preclinical, Female, Graft Rejection/complications, Graft Rejection/epidemiology, Graft Survival/drug effects, Immunosuppressive Agents/administration & dosage, Immunosuppressive Agents/adverse effects, Incidence, Injections, Intramuscular, Keratoplasty, Penetrating, Prodrugs/administration & dosage, Prodrugs/adverse effects, Rats, Rats, Inbred BN, Rats, Inbred Lew
Pubmed
Web of science
Create date
29/08/2013 15:17
Last modification date
20/08/2019 14:39
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