Prolonged corticosteroid treatment exerts transient inhibitory effect on prostaglandin E2 release from rabbits' eyes

Abstract

In humans, the retina and choroid (the photoreceptor and its vascular layers, respectively), are affected by an immunogenic inflammatory reaction--uveitis, associated with excessive levels of prostaglandin E2 (PGE2), and treated for prolonged periods with corticosteroids, known for their inhibitory effect on prostaglandins (PGs) production. In order to assess whether this drug retains its inhibitory effect during chronic use, we investigated the effect of long-term systemic administration of corticosteroids on PGE2 release by the choroid and retina of rabbits' eyes. We used eyes traumatized by laser irradiation, in which the inflammatory reaction is associated with an enhanced PGE2 in vitro release by the choroid-retina throughout a 2-week period; levels peaked on days 1 and 7 to values 2.2- and 5.5-fold, respectively, greater than baseline. Systemic corticosteroid administration to laser-exposed rabbits curtailed the excessive PGE2 release during the first post-laser week; later the amounts released progressively increased to levels 5.5-fold higher than baseline (day 14), whereas in the corresponding untreated laser group, levels were significantly lower. PGE2 tissue content on days 7 and 14 in steroid-treated and untreated laser groups were similarly elevated. We conclude that during prolonged systemic corticosteroids treatment the steroidal inhibitory effect on enhanced PGE2 formation by the retina-choroid of laser injured eyes is transient; it is evident during the early phase following drug administration, whereas later excessive PGE2 release is resumed.