17β-estradiol (βE2) protects human retinal Müller cell against oxidative stress in vitro: Evaluation of its effects on gene expression by cDNA microarray

17 beta-estradiol (beta E-2) is an effective neuroprotectant against hydrogen peroxide (H2O2)-induced retinal neuronal cell death and light-induced photoreceptor degeneration. Muller cells are the principal macroglia responsible for supporting retinal neuronal survival, information processing and removing metabolic waste. However, the role of beta E-2 on human Muller cells is unclear. In this study, the effects of beta E-2 on human Muller cell survival and gene expression were examined. Our data revealed that beta E-2 is able to increase human Muller cell viability after exposure to H2O2 through inhibition of apoptosis. Microarray analysis revealed significant changes in the expression of 69 genes (total of 21,324 genes screened) in cultured human Muller cells 6 h after beta E-2 treatment. Four of the beta E-2-responsive genes [thrombospondin 1 (TSPI), mitogen-activated protein kinase kinase kinase 3 (MAP3K3), large conductance calcium-activated potassium channel beta 2 subunit (KCNMB2), and SRY (sex-determining region Y)-box 11 (SOX11)] were validated by both real-time qRT-PCR and semi-quantitative RT-PCR. Interestingly, exposure of human Muller cells to beta E-2 increased pigment epithelium-derived factor (PEDF) gene expression as measured by both RT-PCR and real time qRT-PCR. Our data demonstrate, for the first time, that beta E-2 protects cultured human Muller cells against H2O2-induced cell death through the inhibition of apoptosis. This protective effect may operate through regulation of genes, such as TSP1, MAP3K3, SOX11, TSP1, and PEDF, and may in turn exert an important role in protecting retinal neurons. (c) 2005 Wiley-Liss, Inc.