Vascular endothelial growth factor/vascular permeability factor (VEGF) in diabetic retinopathy

Purpose. We have previously shown that VEGF immunoreactivity is increased in diabetic retinal vessels compared to non-diabetics (Lutty et al, IOVS 3.5: 1995, 1994). In this study we sought to determine if the number of VEGF positive vessels is related to decreased vascularity and presumed retinal hypoxia. We also correlated increased diffusion of human serum albumin (HSA) with VEGF immunoreactivity because VEGF can induce vascular permeability. VEGF is a heparin binding protein, so the relationship between VEGF and heparan sulfate proteoglycan (HSPG) localization was also investigated. Methods. Cryopreserved postmortem eyes from 18 diabetic and 9 nondiabetic, control subjects were sectioned and immunohistochemistry performed with antibodies against VEGF, HSA, HSPG, vWf (von Willebrand's factor) and collagen IV. Sections were examined by light microscopy and the number of positive vessels for each antibody and antibody localizations were determined. Results. The average number of VEGF stained vessels in diabetic retinas was significantly higher than in control retinas (p=0.04). When related to the total number of viable vessels (determined by anti-vWf immunoreactivity), 72% of the diabetic vessels had VEGF immunoreactivity, compared to 33% in controls. In diabetics, albumin leakage (diffuse staining with anti-HSA in and around vessel walls) was observed in 47.1% of vWf-positive vessels as opposed to 32.2% in controls. In diabetics, we also established a positive correlation between the distribution of HSA positive and VEGF positive vessels. In control retinas, no such correlation could be established. HSPG staining seemed to be colocalized with VEGF staining, suggesting that VEGF is binding to HSPG. Conclusions. Our data indicates that VEGF is associated with HSPG in blood vessel walls, probably for the purpose of prolonged VEGF availability. In this study, we observed increased VEGF expression in diabetic retinas and established a correlation between increased VEGF expression and VEGF-mediated events like vascular permeability to macromolecules.