Jaynes C D, Sheedlo H J, Agarwal N, O'Rourke K, Turner J E
Department of Anatomy and Cell Biology, University of North Texas Health Science Center, Fort Worth 76107, USA.
Brain Res Mol Brain Res. 1995 Sep;32(2):329-37. doi: 10.1016/0169-328x(95)00093-8.
Retinal pigment epithelial (RPE) cells secrete a factor(s) which promotes Müller and RPE cell survival and proliferation in vitro. These influences may play developmental and functional roles as well as contribute to ocular pathologies such as proliferative vitreoretinopathy (PVR). In the past few years, a number of immediate early genes (IEGs) have been identified. Many IBGs encode transcription factors, the expression of which is altered by stimuli such as growth factors. Since an RPE-derived factor(s) elicits proliferation of Müller and RPE cells, we investigated the expression of two IEGs, NGFI-A and c-fos, in both cell types after treatment with medium conditioned by the RPE (RPE-CM). We found that Müller and RPE cells had increased levels of NGFI-A mRNA following treatment with RPE-CM; in contrast, only a slight increase in c-fos mRNA was induced in RPE, but not Müller 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 cells in vivo. Specifically, NGFI-A may be the primary target of a second messenger system that is regulated by an RPE-derived factor(s).
视网膜色素上皮(RPE)细胞分泌一种因子,该因子在体外可促进穆勒细胞和RPE细胞的存活与增殖。这些影响可能在发育和功能方面发挥作用,也可能导致诸如增殖性玻璃体视网膜病变(PVR)等眼部疾病。在过去几年中,已鉴定出许多即刻早期基因(IEGs)。许多IEGs编码转录因子,其表达会因生长因子等刺激而改变。由于一种RPE衍生因子可引发穆勒细胞和RPE细胞的增殖,我们研究了用RPE条件培养基(RPE-CM)处理后,这两种细胞类型中两种IEGs(NGFI-A和c-fos)的表达情况。我们发现,用RPE-CM处理后,穆勒细胞和RPE细胞中NGFI-A mRNA水平升高;相比之下,RPE细胞中c-fos mRNA仅略有增加,而穆勒细胞中未增加。对NGFI-A蛋白的免疫标记显示,两种细胞类型中均有核染色,这与RPE-CM处理培养物中mRNA水平的升高相对应。这项体外研究证明了一种潜在机制,通过该机制RPE分泌的因子可能在体内对视网膜细胞发挥自分泌或旁分泌作用。具体而言,NGFI-A可能是由RPE衍生因子调节的第二信使系统的主要靶点。