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P. Chen, V.R. Thandra, G.M. Scicli, P.A. Edwards, A.G. Scicli; Role of Reactive Oxygen Species in Retinal Leukostasis of Diabetic Rats . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1711.
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Early in diabetic retinopathy there is increased arrested leukocytes (leukostasis) and leukocyte–induced capillary plugging in the retina. We hypothesized that reactive oxygen species (ROS) mediate retinal leukostasis in diabetes.
To study whether retinal leukostasis in diabetic rats is altered by treatment with antioxidants.
Rats with streptozotocin–induced diabetes (glycemia ≥250 mg/dl) were divided in three groups (6–8 rats/group): Group 1, untreated diabetic rats; Group 2, diabetic rats treated with a combination of tempol (∼ 70mg/kg/day), a superoxide dismutase mimetic, and N–Acetyl Cysteine. (NAC, ∼ 1g/kg/day), a gluthatione based antioxidant: Group 3, diabetic rats treated with the NAD(P)H oxidase inhibitor apocynin (∼ 45mg/kg/day). All treatments were given in the drinking water. After two weeks of treatment static retinal leukocytes were labeled with acridine orange, visualized with a Scanning Laser Ophthalmoscope and counted. Leukostasis was expressed as 10–5cells/pixels2.
Compared with controls, diabetic rats had increased retinal leukostasis: 0.1± 0.06 vs. 2.3 ± 0.17 (p<0.01). Retinal leukostasis in diabetic rats was decreased by treatment with tempol–NAC to 0.7±0.1 (p<0.001 vs. untreated diabetes) and by treatment with apocynin to 0.3±0.1 (n.s. vs. normal control; p< 0.001 vs. untreated diabetes. Thus inhibition of NAD(P)H oxidase abolished the augmented retinal leukostasis of early diabetes.
Retinal leukostasis in early diabetes is mediated by ROS. The activity of NAD(P)H oxidase is required for leukostasis in the diabetic retina to occur.
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