Induction of cyclooxygenase-2 gene expression in retinal pigment epithelium cells by photoreceptor rod outer segment phagocytosis and growth factors

Retinal pigment epithelium (RPE) cells in culture display selective inducti on of certain early response transcription factors at the onset of photorec eptor rod outer segment (ROS)-specific phagocytosis (Ershov et al., 1996a). Moreover, this response is modulated by prostaglandins. The purpose of thi s study is to Examine the expression of the key enzymes in prostaglandin sy nthesis: cyclooxygenase-1 (COX-1, constitutive) and cyclooxygenase-2 (COX-2 , inducible), during phagocytosis of ROS by RPE cells. Rat RPE cells in pri mary cell culture were fed with a suspension of freshly isolated rat ROS. C OX-1 and COX-2 mRNA expression was studied by quantitative competitive reve rse transcriptase-polymerase chain reaction (RT-PCR). During phagocytosis o f ROS by RPE cells, RT-PCR revealed an increase in mRNA expression of COX-2 , but not of COX-1, COX-2 was also induced by the phospholipid growth facto r lyso-phosphatidic acid (LPA) and by the peptide growth factors platelet d erived growth factor (PDGF), basic fibroblast growth factor (FGF), and tran sforming growth factor (TGF beta), but not nerve growth factor (NGF). Induc tion of COX-2 by ROS phagocytosis and growth factors through the modulation of prostanoid synthesis may play an important role in the regulation of ce ll functions associated with photoreceptor cell renewal. (C) 1999 Wiley-Lis s, Inc.