Gene Expression Changes in Retinal Müller (Glial) Cells Exposed to Elevated Pressure

Abstract

Purpose: Retinal Müller (glial) cells undergo “reactive gliosis”, a stress response that is accompanied by changes in their morphology and upregulation of various cellular markers. Reactive gliosis is seen in many retinal diseases and conditions; however, it is not known whether it is a common, stereotypic response or the nature of the response varies with the type of retinal stress. To address this question, we have examined gene expression changes in Müller cells exposed to elevated pressure.Materials and Methods: Rat Müller cells (rMC-1) were exposed to elevated pressure, and RNA was extracted and analyzed using Affymetrix GeneChip microarrays to identify pressure-responsive genes.Results: Analysis of microarray data showed that at 6 h, 186 genes had > 1.5-fold change with FDR < 0.01. Of these, 62 genes were up-regulated while 124 genes were down-regulated. At 24 h, 73 genes changed > 1.5-fold. Of these, 37 genes were up-regulated while 36 genes were down-regulated. Ingenuity canonical pathway analysis showed that several signaling and metabolic pathways were significantly changed in Müller cells under high pressure. In addition, among up- and down-regulated genes, we identified eight genes—areg, bmp4, cyp1b1, gpnmb, herc2, msh2, heph, and selenbp1, that have been directly or indirectly associated with elevated intraocular pressure. Two genes, areg and gpnmb, further showed time-dependent changes in mRNA and protein expression.Conclusion: The results show that Müller cells in vitro respond to elevated pressure by differential regulation of expressed genes. The transcriptional profile is different from that seen with hypoxia, which indicates that Müller cells respond differentially to different microenvironmental changes in the retina.