Protection against hydrogen peroxide-induced cell death in cultured human retinal pigment epithelial cells by 17β-estradiol: A differential gene expression profile

It has been demonstrated that estrogen receptors are present in the retinal pigment epithelium (RPE) - choroids complex regardless of sex. This suggests that estrogen could play a functional role in the outer retina, especially the RPE. To gain further insights on the molecular mechanisms differentially activated by 17β-estradiol (βE2) in RPE cells, we investigated gene expression changes in response to βE2 in cultured RPE cells using cDNA microarray technology. A total of 47 genes among 21,329 human genes are significantly altered in response to βE2 treatment in RPE cells. Among these 47 altered genes, 34 are up-regulated and 13 are down-regulated by βE2. The products of 34 genes have a known or suspected function. These functions belong to various categories, including caspases; extracellular matrix proteins; metabolism pathway components; GTP/GDP exchangers and G-protein GTPase activity modulators; transcription activators and repressors. Six genes which may contribute to the unique functions of the RPE cells have been validated by both quantitative real-time reverse transcription (RT)-PCR and semi-quantitative RT-PCR. In addition, we also demonstrated that βE2 quenches H₂O₂-induced up-regulation of apoptosis-related protein, and protects RPE cell degeneration. These results indicate that estrogen regulates functions of RPE cells and is involved in the maintaining and survival of RPE cells during oxidative stress, and its deficiency during menopause period may be a factor contributing to the development of age-related macular degeneration in elderly women.