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

Abstract

Retinal pigment epithelium (RPE) cells in culture display selective induction of certain early response transcription factors at the onset of photoreceptor rod outer segment (ROS)-specific phagocytosis (Ershov et al., 1996a). Moreover, this response is modulated by prostaglandins. The purpose of this study is to examine the expression of the key enzymes in prostaglandin synthesis: cyclooxygenase-1 (COX-1, constitutive) and cyclooxygenase-2 (COX-2, inducible), during phagocytosis of ROS by RPE cells. Rat RPE cells in primary cell culture were fed with a suspension of freshly isolated rat ROS. COX-1 and COX-2 mRNA expression was studied by quantitative competitive reverse transcriptase-polymerase chain reaction (RT-PCR). During phagocytosis of 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 factor lyso-phosphatidic acid (LPA) and by the peptide growth factors platelet derived growth factor (PDGF), basic fibroblast growth factor (FGF), and transforming growth factor (TGFbeta), but not nerve growth factor (NGF). Induction of COX-2 by ROS phagocytosis and growth factors through the modulation of prostanoid synthesis may play an important role in the regulation of cell functions associated with photoreceptor cell renewal.