Ischemia increases prostaglandin H synthase-2 levels in retina and visual cortex in piglets

Background: Ischemia increases levels of prostaglandin H synthase-2 (PGHS-2 ) in neonatal brain and cerebral vasculature, but effects on the developing visual system are unknown. We examined the effects of ischemia on PGHS-2 m RNA and protein levels in the retina and visual cortex in anesthetized pigl ets. Methods: Ten minutes of complete retinal and brain ischemia was induce d by increasing intracranial pressure. After 2-12 h of reperfusion, samples of retina and visual cortex were collected for determinations of levels of PGHS-2 mRNA (RNase protection assay) or protein (immunohistochemistry and western blotting). Tissues also were obtained from control animals. Results : Levels of PGHS-2 mRNA were undetectable in control animals but showed a d ramatic increase at 2-4 h in the cortex and retina in animals exposed to is chemia. Detectable but limited PGHS-2 immunoreactivity (IR) was present in the retina and visual cortex from control animals. In piglets not subjected to ischemia, PGHS-2 IR was localized mainly to the outer limiting membrane and to the Muller cells. Ischemia induced a marked increase in PGHS-2 IR i n the neural retina, with the greatest increase in the photoreceptor layer. PGHS-2 levels in whole retina also increased at 8 h after ischemia. In the intact visual cortex PGHS-2 IR was evident in layers II and V. Ischemia in creased the intensity of IR in layers II/III as well as layer V. Conclusion s: Detectable amounts of PGHS-2 protein are present in the piglet retina an d visual cortex under normal conditions, but levels are markedly increased 8-12 h after ischemic stress. Enhanced PGHS-2 levels after ischemic stress may contribute to delayed pathological changes of the visual system in the neonate.