Abstract
Introduction: :
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.
Purpose: :
To study whether retinal leukostasis in diabetic rats is altered by treatment with antioxidants.
Methods: :
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.
Results: :
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.
Conclusions: :
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.
Keywords: diabetic retinopathy • antioxidants • inflammation