Photoreceptor phagocytosis selectively activates PPAR gamma expression in retinal pigment epithelial cells

Phagocytosis of tips of rod outer segments (ROS) by retinal pigment epithel ial (RPE) cells is vitally important for maintaining structural and functio nal integrity of the retina. We previously reported that receptor-mediated specific phagocytosis of ROS induces expression of early response genes cod ing for transcription factors. Here we study the expression of peroxisome p roliferator-activated receptors (PPAR) -alpha, -delta (beta) and -gamma dur ing ROS phagocytosis of rat RPE cells in primary cell culture, using compet itive quantitative RT-PCR. During phagocytosis of ROS (but not of latex par ticles) by RPE cells, RT-PCR revealed a transient increase in PPAR gamma mR NA expression, that peaked at 4-6 hr. We sequenced and described two altern atively spliced variants of rat PPAR gamma: rPPAR gamma 1a and rPPAR gamma 1b. Both of these, along with the recently described rPPAR gamma 2 were ind uced by ROS phagocytosis. PPAR alpha and PPAR delta mRNA expression was als o detected in RPE cells, but the level of expression did not change during ROS phagocytosis. All-trans-retinoic acid and prostaglandin E-2 (PGE(2)) se lectively potentiated both basal and ROS-phagocytosis-induced PPAR gamma ex pression. All-trans-retinoic acid had the opposite inhibitory effect on PPA R alpha and PPAR delta expression. Cycloheximide had a dual action on PPAR gamma expression in RPE cells: it enhanced expression under basal condition s but repressed expression induced by ROS phagocytosis. It also stimulated expression of PPAR alpha. but had no effect on PPAR delta. Selective activa tion of PPAR gamma may play an important role in regulating the expression of target genes that are involved in lipid and fatty acid metabolism in the photoreceptor renewal process. (C) 2000 Wiley-Liss, Inc.