Evaluation of a topical cyclosporine A prodrug on corneal graft rejection in rats
| Autor: | Jean-Louis BOURGES, Lallemand F, Agla E, Besseghir K, Jm, Dumont, BenEzra D, Gurny R, Behar-Cohen F |
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| Rok vydání: | 2006 |
| Předmět: |
Graft Rejection
Administration Topical Incidence Corneal Edema Graft Survival Drug Evaluation Preclinical Cyclosporins Injections Intramuscular Drug Administration Schedule Rats Corneal Opacity Rats Inbred Lew Rats Inbred BN Cyclosporine Animals Female Prodrugs Immunosuppressive Agents Keratoplasty Penetrating |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1090-0535 |
| Popis: | 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).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.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.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. |
| Databáze: | OpenAIRE |
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