Expression and role of the early-response gene Oxr1 in the hyperoxia-challenged mouse retina
Expression and role of the early-response gene Oxr1 in the hyperoxia-challenged mouse retina
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DOI：
10.1167/iovs.08-1722
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发表时间：
2008-10-01
影响因子：
4.4
通讯作者：
Stone, Jonathan
中科院分区：
文献类型：
--
作者：
Natoli, Riccardo;Provis, Jan;Stone, Jonathan
目的。目的：检测小鼠视网膜对持续高氧的反应。持续暴露(在C57BL/6J小鼠中为7-14天)后，高氧对光感受器有毒性，但已有报道在短期暴露后增强光感受器功能。方法：分别在75%氧暴露0、3、7、14和35天后，对易高氧的C57BL/6J小鼠和耐高氧的BALB/CJ小鼠的视网膜进行检查。应用定量聚合酶链式反应、原位末端标记法和免疫组织化学技术追踪早期反应潜在保护性基因Oxr1的表达规律和表达部位。结果在C57BL/6J视网膜中，Oxr1在暴露3d时表达上调，与该品系耐高氧的早期阶段一致，14d时降至对照水平以下，此时感光细胞已经开始退化。相比之下，与压力相关的基因GFAP仅在7至14天上调。免疫组织化学显示OXr1在光感受器外节的内侧有表达，但随着光感受器的凋亡，OXr1集中在细胞核内，证实了BALB/CJ小鼠光感受器对高氧耐受持续到14d的报道，相应地，OXr1在外节的表达上调持续到14d。结论观察到的Oxr1的表达模式表明，该基因与抵抗高氧攻击有关，并且作用于外节水平。视网膜对高氧的反应可能构成急性和慢性阶段，在这些阶段，光感受器首先对氧化损伤具有抵抗力，然后容易受到氧化损伤。了解这种双相反应对于了解氧在视网膜营养不良进展中的作用可能很重要。
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.