17β-estradiol (βE2) protects human retinal Müller cell against oxidative stress in vitro: Evaluation of its effects on gene expression by cDNA microarray
✍ Scribed by Chao Li; Yuhong Tang; Feng Li; Sean Turner; Kong Li; Xiaohong Zhou; Michael Centola; Xiaorong Yan; Wei Cao
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 555 KB
- Volume
- 53
- Category
- Article
- ISSN
- 0894-1491
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✦ Synopsis
Abstract
17β‐estradiol (βE~2~) is an effective neuroprotectant against hydrogen peroxide (H~2~O~2~)‐induced retinal neuronal cell death and light‐induced photoreceptor degeneration. Müller cells are the principal macroglia responsible for supporting retinal neuronal survival, information processing and removing metabolic waste. However, the role of βE~2~ on human Müller cells is unclear. In this study, the effects of βE~2~ on human Müller cell survival and gene expression were examined. Our data revealed that βE~2~ is able to increase human Müller cell viability after exposure to H~2~O~2~ through inhibition of apoptosis. Microarray analysis revealed significant changes in the expression of 69 genes (total of 21,324 genes screened) in cultured human Müller cells 6 h after βE~2~ treatment. Four of the βE~2~‐responsive genes [thrombospondin 1 (TSP1), mitogen‐activated protein kinase kinase kinase 3 (MAP3K3), large conductance calcium‐activated potassium channel β2 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 Müller cells to βE~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 βE~2~ protects cultured human Müller cells against H~2~O~2~‐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. © 2005 Wiley‐Liss, Inc.