The effect of selective cyclooxygenase-2 inhibitor on corneal angiogenesisin the rat.

PURPOSE. Eicosanoids that are present in inflamedtissues are thought to play a significant role in angiogenesis. Cyclooxygenase,a key enzyme in eicosanoid synthesis, has recently been shown to exist intwo isoforms: the constitutive COX-1 and the inducible COX-2. This study wasundertaken to determine the role of COX-2 in the corneal angiogenic response. METHODS. Angiogenesis in the rat cornea was provoked by chemical cautery.Either NS-398, a selective COX-2 inhibitor, or indomethacin, a non-selectiveCOX inhibitor, was applied topically 3 times daily for 4 days. Neovascularizationwas quantitated by digital image analysis in corneal flat preparations. Totest their inhibitory effects on eicosanoid synthesis, normal or cauterizedcorneas were incubated in the culture medium with the inhibitor. ProstaglandinE2 in the medium was assayed using an enzyme-linked immunosorbent assay. RESULTS. Both NS-398 and indomethacin significantly inhibited corneal neovascularizationwith the % inhibition of 36.4 ± 9.6%, and 38.5 ± 9.0%, respectively,when applied topically at a concentration of 0.1% (p < .001). Neither reducedthe angiogenic response at a concentration of 0.01% or below. PGE[sub 2] production in the cauterized cornea was 2.0 times higher than that in thecontrols. In normal corneas, indomethacin inhibited PGE[sub 2] synthesisby 80%, whereas NS-398 inhibited it by no more than 20%. In contrast, in injuredcorneas, both indomethacin and NS-398 inhibited PGE[sub 2] synthesisin a similar fashion, with a maximal inhibition rate of 75 to 80%. CONCLUSIONS. Our results suggest that COX-2 induction in cauterized corneasincreases the level of eicosanoids, which result in corneal angiogenesis. [ABSTRACT FROM AUTHOR]