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L. M. Hjelmeland, A. Fujikawa, S. L. Oltjen, Z. Smit-McBride; Aging of the Estrogen Signaling Axis of the Mouse Posterior Pole. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5555. doi: https://doi.org/.
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Previous studies have examined possible roles for estrogen as a neurotrophic factor in the retina/RPE. Estrogen acts through a complex family of receptors, some of which exhibit age-related changes in expression levels. This study examines the expression of these receptors in the retina/RPE. The potential role of epigenetics in age-related changes of gene expression was also specifically examined.
Balb/cBy mice (male and female) at 6 weeks and 24 months of age were obtained from the NIA. The retina and the RPE/choroid were separately dissected after which samples of DNA and RNA were prepared. RNA samples were pooled and examined for gene expression using Taqman assays. DNA samples were treated with Na bisulfite, amplified by PCR, then cloned and sequenced to quantify DNA methylation.Gene expression at the histological level was examined by immunohistochemistry and in situ hybridization on paraffin sections from PFA fixed eyes.
Out of a larger panel of genes which were studied, we found significant expression of estrogen receptor alpha (ER alpha), estrogen related receptor, alpha (ERR alpha) and the G protein-coupled estrogen receptor 1 (Gpr-30). Immunohistochemistry in each case showed localization in the nucleus of the RPE as well as other locations.Comparing the 24 month data with the 6 week data we found significant age-related reduction in the expression of ERR alpha in the retina and RPE/choroid of the male but only in the retina of the female.
Although the ER alpha gene is epigenetically silenced in a variety of tissues, we found no such evidence for ER alpha silencing in the posterior pole of the mouse eye. ERR alpha has not been previously studied for age-related changes in gene expression or for epigenetic regulation. ERR alpha, however, is thought to play a major role in the regulation of the oxidative stress response and mitochondrial biogenesis. Our findings support additional study on the expression of the ERR alpha gene in the posterior pole of the eye.
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