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This Article Full Text Full Text (PDF) All Versions of this Article: iovs.08-1722v1 49/10/4561    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Natoli, R. Articles by Stone, J. PubMed PubMed Citation Articles by Natoli, R. Articles by Stone, J.

Expression and Role of the Early-Response Gene Oxr1 in the Hyperoxia-Challenged Mouse Retina

¹From the ARC Centre of Excellence for Visual Sciences and the ²Visual Sciences Group, Research School of Biological Sciences, Australian National University, Canberra, Australia; and ³Save Sight Institute, University of Sydney, Sydney, Australia.

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.