MULLER AND RETINAL-PIGMENT EPITHELIAL (RPE) CELL EXPRESSION OF NGFI-AAND C-FOS MESSENGER-RNA IN RESPONSE TO MEDIUM CONDITIONED BY THE RPE

Retinal pigment epithelial (RPE) cells secrete a factor(s) which promo tes Muller and RPE cell survival and proliferation in vitro. These inf luences may play developmental and functional roles as well as contrib ute to ocular pathologies such as proliferative vitreoretinopathy (PVR ). In the past few years, a number of immediate early genes (IEGs) hav e been identified. Many IBGs encode transcription factors, the express ion of which is altered by stimuli such as growth factors. Since an RP E-derived factor(s) elicits proliferation of Muller and RPE cells, we investigated the expression of two IEGs, NGFI-A and c-fos, in both cel l types after treatment with medium conditioned by the RPE (RPE-CM). W e found that Muller and RPE cells had increased levels of NGFI-A mRNA following treatment with RPE-CM; in contrast, only a slight increase i n c-fos mRNA was induced in RPE, but not Muller cells. Immunolabeling for NGFI-A protein revealed nuclear staining in both cell types which corresponded with the increased mRNA levels in RPE-CM-treated cultures . This in vitro study demonstrates a potential mechanism by which RPE- secreted factors may exert autocrine or paracrine effects on retinal c ells in vivo. Specifically, NGFI-A may be the primary target of a seco nd messenger system that is regulated by an RPE-derived factor(s).