Jivabhai Patel Shamin, Bany-Mohammed Fayez, McNally Lois, Valencia Gloria B, Lazzaro Douglas R, Aranda Jacob V, Beharry Kay D
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of California-Irvine, Irvine, California, United States.
Department of Ophthalmology, State University of New York, Downstate Medical Center, New York, New York, United States State University of New York Eye Institute, New York, New York, United States.
Invest Ophthalmol Vis Sci. 2015 Feb 10;56(3):1665-77. doi: 10.1167/iovs.14-15321.
Frequent, brief intermittent episodes of hypoxia (IH) during hyperoxia increase reactive oxygen species in the immature retina with compromised antioxidant systems, thus leading to oxygen-induced retinopathy (OIR). We examined the hypothesis that early exposure to a mimetic of superoxide dismutase (SOD), the first line of defense against oxidative stress, will decrease IH-induced reactive oxygen species (ROS) and prevent severe OIR in our rat model.
To test this hypothesis, newborn rats (P0) were exposed to IH consisting of alternating cycles of 50% O₂ with brief hypoxia (12% O₂) until P14 during which they were treated with a single daily intraperitoneal (IP) dose of MnTBAP (a SOD mimetic) at 1.0, 5.0, or 10.0 mg/kg on P0, P1, and P2. A saline-treated group served as vehicle controls. Groups were analyzed following IH at P14 or allowed to recover in room air (RA) until P21. Control littermates were raised in RA with all conditions identical except for inspired O₂. Ocular assessment of OIR severity, oxidative stress, angiogenesis, antioxidant activity, and oxidative phosphorylation (OXPHOS) were conducted at P14 and P21.
Collectively, the data show increased oxidative stress and angiogenesis with MnTBAP, which was associated with photoreceptor damage, retinal characteristics consistent with severe OIR, and changes in genes regulating OXPHOS.
In the setting of IH, the use of exogenous SOD mimetics must be combined with H₂O₂ scavengers in order to prevent photoreceptor damage and severe OIR.
高氧期间频繁、短暂的间歇性缺氧（IH）会增加抗氧化系统受损的未成熟视网膜中的活性氧，从而导致氧诱导性视网膜病变（OIR）。我们检验了这样一种假设，即早期暴露于超氧化物歧化酶（SOD）模拟物（抗氧化应激的第一道防线）会减少IH诱导的活性氧（ROS），并在我们的大鼠模型中预防严重的OIR。
为了验证这一假设，新生大鼠（出生第0天）暴露于由50%氧气与短暂缺氧（12%氧气）交替循环组成的IH环境中，直至出生第14天，在此期间，它们在出生第0天、第1天和第2天每天接受一次腹腔内（IP）注射剂量为1.0、5.0或10.0 mg/kg的MnTBAP（一种SOD模拟物）。一个生理盐水处理组作为载体对照。在出生第14天进行IH后对各组进行分析，或者让它们在室内空气（RA）中恢复至出生第21天。对照同窝幼崽在RA中饲养，除了吸入的氧气外，所有条件均相同。在出生第14天和第21天对OIR严重程度、氧化应激、血管生成、抗氧化活性和氧化磷酸化（OXPHOS）进行眼部评估。
总体而言，数据显示MnTBAP会增加氧化应激和血管生成，这与光感受器损伤、与严重OIR一致的视网膜特征以及调节OXPHOS的基因变化有关。
在IH情况下，使用外源性SOD模拟物必须与过氧化氢清除剂联合使用，以防止光感受器损伤和严重的OIR。
