Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability is mediated by intercellular adhesion molecule-1 (ICAM-1)

Two prominent vascular endothelial growth factor (VEGF)-induced retinal eff ects are vascular permeability and capillary nonperfusion. The mechanisms b y which these effects occur are not completely known. Using a rat model, we show that intravitreous injections of VEGF precipitate an extensive retina l leukocyte stasis (leukostasis) that coincides with enhanced vascular perm eability and capillary nonperfusion. The leukostasis is accompanied by the up-regulation of intercellular adhesion molecule-1 expression in the retina . The inhibition of intercellular adhesion molecule-1 bioactivity with a ne utralizing antibody prevents the permeability and leukostasis increases by 79% and 54%, respectively. These data are the first to demonstrate that a n onendothelial cell type contributes to VEGF-induced vascular permeability. Additionally, they identify a potential mechanism for VEGF-induced retinal capillary nonperfusion.