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V.R. Thandra, P. Chen, A. Abbas, P.A. Edwards, A.G. Scicli; Role of Oxidative Stress in Angiotensin II Induced Retinal Leukostasis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1709.
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© ARVO (1962-2015); The Authors (2016-present)
The increased arrested leukocytes (leukostasis) observed in the retina of early diabetic rats is markedly decreased with inhibition of angiotensin II (ARVO, 2003). Angiotensin II (Ang II) can increase reactive oxygen species (ROS), in part by activation of NAD(P)H oxidase. We hypothesize that Ang II increases retinal leukostasis and that it acts via ROS.
To determine: 1. Whether intravitreal (ivt) Ang II induces retinal leukostasis; and 2. Whether Ang II–induced leukostasis is affected by treatment with a combination of tempol, a superoxide dismutase mimetic, and N–Acetyl–Cysteine (NAC), a gluthatione based antioxidant, and also by treatment with apocynin, a NAD(P)H oxidase inhibitor.
Male Long–Evans rats were injected ivt with Ang II (20ug in 2ul solution). The Ang II–injected rats were divided into three groups: 1. Untreated; 2. Treated with tempol (∼ 70mg/kg/day) and NAC (∼ 1g/kg/day); 3. Treated with apocynin (∼ 45mg/kg/day). Drugs were given in the drinking water, beginning 72 hours before ivt injections. Leukostasis was evaluated 48 hours after ivt injections by acridine orange labeling of leukocytes followed by counting static retinal leukocytes in a 40 degree field around the optic nerve using a scanning laser ophthalmoscope. Leukostasis is expressed as 10–5cells/pixel2
Ang II increased retinal leukostasis from 0.5±0.1 in controls to 2.1±0.5 (p< 0.01). Ang II–induced retinal leukostasis was decreased by treatment with tempol+NAC to 0.7±0.2 (n.s. vs. controls; p<0.02 vs. Ang II alone), and by apocynin to 0.4±0.2 (n.s. vs. controls; p< 0.02 vs. Ang II alone). Thus, both treatments abolished Ang II–induced retinal leukostasis.
Increasing the intravitreal concentration of Ang II induces retinal leukostasis, which appears mediated by ROS. These effects of Ang II require NAD(P)H oxidase activity, suggesting that it acts by increasing superoxide generation by NAD(P)H oxidase.
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