Intravitreal Administration of VEGF Trap Suppresses Vascular Leak in the Retinas of Diabetic Rats

Abstract

Purpose: : To evaluate whether intravitreal administration of the VEGF Trap (a potent VEGF inhibitor which binds all VEGF–A isoforms and placental growth factor) can reverse breakdown of the blood–retinal barrier in diabetic rats.

Methods: : Diabetes was induced in adult, male Sprague–Dawley rats by intraperitoneal injection of Streptozotocin (STZ, 60 mg/kg). Blood glucose levels were monitored 24 ∼ 48 hours later and weekly thereafter. All animals used in the following experiment maintained blood glucose levels in excess of 250 mg/dL. One week after induction of diabetes, VEGF Trap (3 mcg / 3 mcL), human Fc (3 mcg / 3 mcL), or a vehicle solution was injected intravitreally. The effect of treatment on retinal vascular permeability was determined 48 hours and 7 days later by measuring retinal content of extravasated Evans Blue (EB) dye, as described previously. Serum levels of VEGF Trap were measured by ELISA 2 days after intravitreal injection.

Results: : Compared with non–diabetic controls, the eyes of diabetic rats showed a 2∼3–fold increase in EB content, indicative of increased retinal vascular permeability. Compared to vehicle or hFc treated diabetic controls, intravitreal administration of VEGF Trap significantly reduced EB extravasation at day 2 (p < 0.05) and day 7 (p < 0.001), respectively, to levels characteristic of non–diabetic rats. There was no detectable unbound VEGF Trap in the serum 2 days following intravitreal administration.

Conclusions: : Intravitreal administration of VEGF Trap significantly reduces retinal vascular permeability in diabetic rats. These results indicate that intravitreal administration of VEGF Trap may prove useful in the treatment of diabetic retinopathy and macular edema.

Keywords: diabetic retinopathy • growth factors/growth factor receptors