INCREASED SYNTHESIS OF SPECIFIC EICOSANOIDS IN REJECTED CORNEAL GRAFTS

Purpose. Corneal injury stimulates the formation of both prostaglandin s (PG) and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), the major lipoxygenase metabolite. The purpose of this study was to investigate the metabolism of arachidonic acid (AA) in a model of corneal graft re jection. Methods. Corneal tissue from Dutch belted rabbits was transpl anted to vascularized corneas of New Zealand white rabbits. Rejected c orneas were removed at the endstage of allograft failure. The allograf t, the host corneal rim, the contralateral control corneal rim of equa l size and normal Dutch belted cornea from the same site as the allogr aft were incubated with 0.25 mu Ci [H-3]AA and the released eicosanoid s were analyzed by high-performance liquid chromatography. Results. Th e host corneal rims, adjacent to the failed allografts, produced up to five times as much 12(S) -hydroxyeicosatetraenoic acid (12(S)-HETE) a s contralateral control corneal rims. Additionally, prostaglandin E(2) (PGE(2)) formation in the host rims increased 100% above controls, an d 12(S)-HETE and PGE(2) synthesis in the rejected corneal graft also i ncreased. 12(R)-HETrE, an endogenous corneal angiogenic factor, was no t detected in rejected corneas. Conclusions. The results point to the importance of selective AA pathways as the source of key inflammatory components found in rejected allografts.