Inhibition of cyclooxygenase-2, but not cyclooxygenase-1, reduces prostaglandin E2 secretion from diabetic rat retinas

Up-regulation of cyclooxygenase-2 occurs in retinal cells during the early onset of diabetic retinopathy. Under these conditions, prostaglandin production is elevated, which in turn leads to an increased expression of vascular endothelial growth factor (VEGF)-a growth factor implicated in vascular leakage and neovascularization. In this ex vivo study, we tested whether cyclooxygenase-1 or cyclooxygenase-2 is responsible for diabetes-induced secretion of prostaglandin E-2 from isolated rat retinas. Celecoxib, a selective cyclooxygenase-2 inhibitor, significantly inhibited prostaglandin E-2 secretion, whereas SC560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole], a selective cyclooxygenase-1 inhibitor, had no inhibitory effect. This result suggests that the enzymatic activity of cyclooxygenase-2, but not cyclooxygenase-1, results in prostaglandin E-2 secretion under diabetic conditions. (C) 2004 Elsevier B.V. All rights reserved.