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Jullia Rosdahl, Guorong Li, Jianming Qiu, Pedro Gonzalez, Pratap Challa; FOXOs in the Mouse Visual System. Invest. Ophthalmol. Vis. Sci. 2013;54(15):292.
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The FOXO family of transcription factors regulates genes involved in aging, oxidative stress, and metabolism, processes involved in the pathogenesis of glaucoma. The purpose of this study is to determine whether the expression profile of the FOXO family members is consistent with a role in glaucomatous vision loss.
Antibodies for FOXO1, FOXO3, and FOXO4 were used to identify protein expression and localization in retinal and brain sections of pup, 2 month old, 6 month old, and 12 month old mice, using Immunohistochemistry and Western Blotting techniques. Aged and glaucomatous human retinas were also analyzed. Real time PCR was used to assess RNA expression of the FOXO family members and their known regulators, in mouse tissues.
FOXO1 and FOXO3 proteins are expressed in the retina and brain in pup, 2 month old, 6 month old, and 12 month old mice. Very low levels of FOXO4 expression were detected by both Western Blotting and PCR techniques. In the retina, the highest expression of FOXO1 and FOXO3 is seen in the retinal ganglion cell layer. In the brain, the highest expression is seen in the cerebellum. These proteins localize to a subset of cells in the cerebellum, the cortex, the superior colliculus and inferior colliculus. Using real time PCR to quantify the expression at the time points tested, the highest expression is seen in 2-month-old mice. In human retina, FOXO1 and FOXO3 expression is highest in the retinal ganglion cell layer, in both aged and glaucomatous tissue.
FOXO1 and FOXO3, but not FOXO4, are expressed in the visual system of mice. The FOXO proteins localize to the retinal ganglion cell layer, in mice as well as humans. Their expression pattern supports a role for this family of transcription factors in regulating aging, oxidative stress, and metabolism in the cells affected by Glaucoma.
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