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Publication : Expression and role of the early-response gene Oxr1 in the hyperoxia-challenged mouse retina.

First Author  Natoli R Year  2008
Journal  Invest Ophthalmol Vis Sci Volume  49
Issue  10 Pages  4561-7
PubMed ID  18539939 Mgi Jnum  J:141791
Mgi Id  MGI:3819741 Doi  10.1167/iovs.08-1722
Citation  Natoli R, et al. (2008) Expression and role of the early-response gene Oxr1 in the hyperoxia-challenged mouse retina. Invest Ophthalmol Vis Sci 49(10):4561-7
abstractText  PURPOSE: To examine the response of mouse retina to sustained hyperoxia. Hyperoxia is toxic to photoreceptors after sustained exposure (7-14 days in the C57BL/6J mouse) but has been reported to enhance photoreceptor function after short-term exposure. METHODS: Retinas from the hyperoxia-vulnerable C57BL/6J mouse and from the hyperoxia-resistant BALB/cJ mouse were examined after 0, 3, 7, 14, and 35 days' exposure to 75% oxygen. Quantitative PCR, TUNEL, and immunohistochemical techniques were used to trace the regulation and site of expression of the early-response, potentially protective gene Oxr1. RESULTS: In the C57BL/6J retina, Oxr1 was upregulated at 3 days of exposure, matching the early period of resistance to hyperoxia in this strain, and fell below control levels at 14 days, when photoreceptor degeneration had begun. By contrast, the stress-related gene GFAP was upregulated only at 7 to 14 days. Immunohistochemistry showed a concentration of Oxr1 in the inner part of photoreceptor outer segments, but, as photoreceptors underwent apoptosis, Oxr1 concentrated in the nucleus, confirming earlier reports that photoreceptors were resistant to hyperoxia until 14 days in the BALB/cJ mouse and, correspondingly, that the upregulation of Oxr1 in outer segments was sustained until 14 days. CONCLUSIONS: The patterns of Oxr1 expression observed suggest that the gene is associated with resistance to hyperoxic challenge and that it acts at the level of the outer segment. The retinal response to hyperoxia may constitute acute and chronic phases in which photoreceptors are first resistant, and then vulnerable, to oxidative damage. Understanding this biphasic response may be important in understanding the role of oxygen in the progress of retinal dystrophy.
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