Vascular Endothelial Growth Factor (VEGF) increases retinal vascular permeability in vivo

Purpose. Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is an important mediator of the intraocular neovascularization common to numerous ischemic retinopathies. Increased vascular permeability frequently accompanies these conditions. Although VEGF is a potent vasopermeability factor in skin, its permeability effects on the retinal vasculature are not well understood. We evaluated retinal vascular permeability in rats following intravitreal and intravenous administration of VEGF. Methods. Sprague-Dawley rats had jugular catheters placed 24 hours prior to each experiment. For intravitreal studies, each rat received a 10ul intravitreal injection of VEGF in one eye and a similar injection of PBS in the contralateral eye. Retinal vascular integrity was evaluated by SLO following the injections. A 30ul bolus of fluorescein was delivered through the catheter after various periods and aqueous and vitreous fluorophotometry were performed 0, 2, 5, 10, 15, 2) and 30 minutes later. For intravenous studies, a VRGF bolus was injected through the catheter and subsequent fluorophotometry performed. Results. Intravitreal injection of VEGF increased retinal vascular permeability in a dose dependent manner attaining levels 2.7 fold higher than control eyes within 5 minutes (final intraocular VEGF = 50ng/ml). The effect was evident at all time points (P<0.007-0.047). No changes in aqueous permeability following intravitreal injection, nor differences in aqueous or vitreal permeability following intravenous administration of VEGF (up to 3ug/rat) were observed. Effects of VEGF pathway inhibitors are currently being studied. Conclusions. These data demonstrate that VEGF can increase retinal vascular permeability in vivo, thus implicat ng VEGF as a potential mediator of retinal exudation and edema in numerous ischemic retinopathies. Consequently, VEGF inhibitors may have a therpautic role in conditions such as diabetic macular edema and central retinal vein occlusion.