The effect of urocanic acid on graft rejection in an experimental model of orthotopic corneal transplantation in rabbits.

BACKGROUND: Urocanic acid (UCA) is a natural component of the stratum corneum of the skin. It has been described as a photoreceptor for ultraviolet B radiation. UCA is present in the skin as a trans-isomer and undergoes UVB irradiation-dependent isomerization from trans-to cis-isomer. An immunosuppressive effect of irradiated UCA, i.e. a mixture of cis- and trans-isomers, has been demonstrated both in vivo and in vitro. The aim of this study was to evaluate an immunosuppressive effect of irradiated UCA on graft rejection in an experimental model of orthotopic corneal transplantation. METHOD: A commercially available UCA was dissolved in salt solution and irradiated by XeCl excimer laser beam in order to obtain a mixture of cis- and trans-isomers. The immunosuppressive effect of irradiated UCA, compared to controls, unirradiated UCA and salt solution, was evaluated in a high-risk orthotopic corneal transplantation model; the agents were administered subconjunctivally to rabbits. RESULTS: The rejection reaction was observed in all animals. The mean graft survival time in rabbits administered salt solution or unirradiated UCA was 20 days and 22 days, respectively. The irradiated solution of UCA significantly (P < 0.01, Mantel-Cox test) prolonged mean graft survival time to 29 days. CONCLUSION: Subconjunctival administration of irradiated UCA prolonged the graft survival time in comparison with unirradiated UCA or salt solution in recipients in a rabbit transplantation model. Although further studies are necessary, UCA seems to be an effective immunosuppressive drug after corneal transplantation.