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J. Cao, H. Song, R.A. Renard, Y. Liu, G.D. Yancopoulos, S.J. Wiegand; Systemic Administration of VEGF Trap Suppresses Vascular Leak and Leukostasis in the Retinas of Diabetic Rats . Invest. Ophthalmol. Vis. Sci. 2005;46(13):446.
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Purpose:To determine whether the VEGF Trap (a potent VEGF inhibitor comprising portions of the ligand binding domains of VEGF receptors 1 and 2 coupled to human Fc), can reverse breakdown of blood–retinal barrier and ameliorate retinal leukostasis in diabetic rats. Methods: Diabetes was induced in male Sprague–Dawley rats by an intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Blood glucose levels were monitored 24 hours later and weekly thereafter, and all animals used in the following experiment maintained blood glucose levels in excess of 250 mg/dL. Two or four weeks after induction of diabetes, VEGF Trap (12.5 mg/kg) or a vehicle solution was administered subcutaneously. The effect of treatment on retinal vascular permeability was determined 48 hours later by measuring retinal content of extravasated Evans Blue (EB) dye, as described previously. The effect of VEGF Trap on retinal leukostasis also was evaluated by perfusion of control and treated animals with fluoresceinated concanavalin A to label adherent leukocytes in the retina. The numbers of leukocytes were counted in flat–mounted retinas under a fluorescence microscope. Results:Compared with non–diabetic controls, the eyes of diabetic rats showed an ∼3–fold increase in the number of adherent leukocytes and a 2∼3–fold increase in EB content, indicative of increased retinal vascular permeability. Compared to vehicle treated diabetic controls, systemic administration of VEGF Trap significantly reduced EB extravasation (p < 0.005) and substantially suppressed leukostasis (p < 0.001) at both 2 and 4 weeks following the induction of diabetes. Conclusions: Systemic administration of VEGF Trap significantly reduces the retinal vascular permeability and leukostasis in diabetic rats. These results indicate that VEGF Trap may prove useful in the treatment of diabetic retinopathy and macular edema. CR: E
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