Biosynthesis of lipoxygenase products by ocular tissues.

The metabolism of arachidonic acid via the lipoxygenase pathway has been investigated in conjunctival and iris tissue taken from eyes of various species. In addition we have also studied two inhibitors of arachidonate metabolism, BW 755 and indomethacin, on albino rabbit ocular tissues. The ocular tissues of most species (monkey, dog, cat, rabbit, guinea-pig and rat) formed lipoxygenase products from exogenous arachidonic acid. The exception was the albino rabbit iris, where no lipoxygenase product was detected. The major lipoxygenase product found was 12-HETE, although 5-HETE and 5,12-diHETE were formed to a lesser extent by the conjunctiva and iris of the Dutch rabbit. The rat ocular tissues and guinea pig conjunctiva also formed 5-HETE. In the conjunctiva of the albino rabbit, indomethacin was a relatively specific inhibitor of the cyclo-oxygenase pathway whereas BW 755 inhibited both the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism. In view of the possible roles of lipoxygenase products in inflammatory reactions and the ability of ocular tissues to synthesize these products, dual inhibitors of cyclo-oxygenase and lipoxygenase pathways may be useful agents to control ocular inflammatory responses.