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Shamin Jivabhai Patel, Fayez Bany-Mohammed, Lois McNally, Gloria B. Valencia, Douglas R. Lazzaro, Jacob V. Aranda, Kay D. Beharry; Exogenous Superoxide Dismutase Mimetic Without Scavenging H2O2 Causes Photoreceptor Damage in a Rat Model for Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(3):1665-1677. doi: https://doi.org/10.1167/iovs.14-15321.
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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.
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