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H. Chen, B. Liu, T. Lucas, A. H. Neufeld; Changes in the Expression of Iron-Regulating Genes in the Aging Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4920.
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Excess iron in CNS tissues contributes to oxidative damage and has been associated with age-related susceptibility in several neurodegenerations. Altered expression of iron-regulating genes and proteins have recently been reported in age-related macular degeneration and in glaucoma. We have examined potential changes in iron homeostasis in the normal aging retina by comparing the expression of iron-regulating genes and proteins in young and aged mice.
mRNA was isolated from young (5 months) and aged (25 months) mice retina. Comparisons using Affymetrix microarray were performed. Differential expression of iron-regulating genes included ferritin, transferrin and transferrin receptor. Expression of these genes was confirmed by real time RT-PCR. In addition, the protein levels of ferritin, transferrin and transferrin receptor were detected by immunohistochemistry and Western blots in retinas from young and aged mice. Furthermore, paraquat-induced oxidative damage of the retina was studied for its effects on iron-regulating genes.
Comparisons from the microarrays suggested increased expression of iron-regulating genes with age. RT-PCR showed that the genes for ferritin light chain, transferrin and transferrin receptor were upregulated in aged mice retina. Immunohistochemistry localized ferritin to the ganglion cell layer (GCL), the inner nuclear layer and the photoreceptors in young mice retina. Transferrin and transferrin receptor were weakly expressed in the GCL in young animals. In the aged retina, the intensities of immunohistochemical labeling for transferrin and transferrin receptor in the GCL were significantly increased. In addtion, transferrin and transferrin receptor appeared in inner nuclear layer cells in aged retina. Western blots also showed that the levels of transferrin and transferrin receptor increased in the retinas of aged mice. Paraquat, which causes oxidative damage in the retina and other tissues, mimicked the increased expression of transferrin and transferrin receptor seen with aging.
The present study demonstrates upregulation of iron-regulating genes and proteins in the retina during normal aging, similar to the changes induced by oxidative stress. An imbalance in iron homeostasis in the retina with age may lead to increased susceptibility to factors underlying retinal degenerations.
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