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A Matsubara, K Tamai, K Tomida, Y Matsuda, H Morita, Y Niwa, D Armstrong, Y Ogura; Protective Effect of Polyethylene Glycol-Superoxide Dismutase on Leukocyte Dynamics in Rat Retinal Microcirculation under Lipid Hydroperoxide-Induced Oxidative Stress . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4532.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Oxidative stress is considered to be one of the major causes of various retinal circulatory disorders. In fact, lipid hydroperoxide (LHP) levels in the vitreous are increased in proliferative diabetic retinopathy, retinopathy of prematurity and Eales' disease. We have previously demonstrated that increased levels of LHP in the vitreous could enhance leukocyte-endothelial interaction in the retinal microcirculation. In the present study, we investigated effect of polyethylene glycol-superoxide dismutase (PEG-SOD) on leukocyte-endothelial interaction in rat retinal microcirculation in vivo following LHP exposure. Methods: Male Brown-Norway rats weighing approximately 250 g were used. LHP(18:2) was made from linoleic acid (LA) with lipoxygenase, and 10µg of LHP dissolved in 5µl of sodium borate buffer (SBB, 0.02M) was slowly injected into the vitreous using a 33-gauge needle. PEG-SOD (5,000 units/kg) was given intravenously 5 minutes before LHP injection. As controls, vehicle-treated rats were given the same amount of unoxidized LA dissolved in 5µl of SBB. At 6, 12, 24 and 48 hours after the LHP injections, we evaluated the flux of rolling leukocytes along the major retinal veins and the number of leukocytes that accumulated in the retinal microvasculature with acridine orange digital fluorography. Results: In LHP-treated rats, leukocyte rolling along the major retinal veins was maximal at 6 hours after LHP injection (11111 cells/min). With PEG-SOD pre-medication, the number of rolling leukocytes was significantly decreased by 95% at 6 hours after LHP injection (60.3 cells/min, p<0.01). No rolling leukocytes were observed in controls. The number of accumulated leukocytes in LHP-treated eyes started to increase at 12 hours (15237 cells/mm2), and peaked at 24hours (919223 cells/mm2). With PEG-SOG pre-medication, the number was significantly reduced by 88 % at 24 hours (11226 cells/mm2, p<0.01). Conclusion: PEG-SOD significantly inhibits both leukocyte rolling and their accumulation in the retinal microcirculation under LHP-induced oxidative stress. These results suggest a therapeutic potential of PEG-SOD on various retinal circulatory disorders.
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