Increased synthesis of specific eicosanoids in rejected corneal grafts

Abstract

Purpose. Corneal injury stimulates the formation of both pros-taglandins (PG) and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), the major lipoxygenase metabolite. The purpose of this study was to investigate the metabolism of arachi-donic acid (AA) in a model of corneal graft rejection.

Methods. Corneal tissue from Dutch belted rabbits was transplanted to vascularized corneas of New Zealand white rabbits. Rejected corneas were removed at the endstage of allograft failure. The allograft, the host corneal rim, the contralateral control corneal rim of equal size and normal Dutch belted cornea from the same site as the allograft were incubated with 0.25 μCi [³H]AA and the released eicosanoids were analyzed by high-performance liquid chromatography.

Results. The host corneal rims, adjacent to the failed allografts, produced up to five times as much 12(S)-hydroxyeicosatet-raenoic acid (12(S)-HETE) as contralateral control corneal rims. Additionally, prostaglandin E₂ (PGE₂) formation in the host rims increased 100% above controls, and 12(S)-HETE and PGE₂ synthesis in the rejected corneal graft also increased. 12(R)-HETrE, an endogenous corneal angiogenic factor, was not 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.

Key Words:

• corneal rejection
• eicosanoid
• 12(S)-hydroxyeico-satctraenoic acid (HETE)
• penetrating keratoplasty
• prostaglandin E₂ (PGE₂)
• rabbit