Scientific article
Open access

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

Published inMolecular vision, vol. 12, p. 1461-1466
Publication date2006-12-02

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 μg/l and 755±319 μg/l on day 2 and 14±34 μg/l and 1318±463 μg/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.

Citation (ISO format)
BOURGES, Jean-Louis et al. Evaluation of a topical cyclosporine A prodrug on corneal graft rejection in rats. In: Molecular vision, 2006, vol. 12, p. 1461–1466.
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Article (Published version)
  • PID : unige:171620
ISSN of the journal1090-0535

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