Impact of Intravitreal Bevacizumab on Accumulation of Vascular Adhesion Protein-1 in Proliferative Diabetic Retinopathy

Abstract

Purpose: : Vascular adhesion protein (VAP)-1, a multifunctional molecule with adhesive and enzymatic properties, is expressed mainly in the vascular endothelial cells of mammals. VAP-1 is known to generate hydrogen peroxide through the enzymatic activity and in turn increase the oxidative stress. The aim of this study is to investigate the effect of intravitreal bevacizumab (IVB), a humanized anti-VEGF monoclonal antibody, on the accumulation of soluble form of VAP-1 (sVAP-1) and oxidative stress in proliferative diabetic retinopathy (PDR).

Methods: : Vitreous samples were collected from 37 eyes of 37 cases with PDR (mean age, 58.8±1.4y/o), who underwent pars plana vitrectomy for prolonged vitreous hemorrhage or tractional retinal detachment involving the macular region at Hokkaido University Hospital from 2006 to 2011. This study was conducted in accordance with the tenets of the Declaration of Helsinki and after receiving approval from the institutional review committee of Hokkaido University Hospital. Of 37 eyes, 14 eyes were received the preoperative IVB (IVB group, 10 male and 4 female, 56.1±2.0y/o) and 23 eyes were not received (non-IVB group, 12 male and 11 female, 60.5±1.8y/o). Protein levels of sVAP-1 and N epsilon-(hexanoyl) lysine (HEL), a marker of oxidative stress, were measured in the vitreous samples by enzyme-linked immunosorbent assay (ELISA).

Results: : Vitreous level of sVAP-1 in IVB group was significantly lower (5.5±1.2ng/ml) compared with that in non-IVB group (9.3±1.2ng/ml, p<0.05). Similarly, the concentration of HEL in the vitreous was significantly reduced in IVB group (4.7±0.6ng/ml) than in control group (8.5±0.9ng/ml, p<0.01). Furthermore, protein concentration of sVAP-1 was positively correlated with HEL in the samples (r=0.42, p<0.01).

Conclusions: : Our data for the first time provide the evidence on the link between VEGF and sVAP-1 in eyes with PDR. The current data suggest that VEGF blockade decreases the concentration of vitreous sVAP-1 and thereby reduces the oxidative stress in PDR eyes.

Keywords: diabetic retinopathy • oxidation/oxidative or free radical damage • vitreous