OBJECTIVE -To evaluate the intravitreous concentration of vascular cell adhesion molecule (VCAM)-1 in diabetic patients with proliferative diabetic retinopathy (PDR) and the relationship of VCAM-1 with vascular endothelial growth factor (VEGF).RESEARCH DESIGN AND METHODS -Serum and vitreous fluid samples were obtained simultaneously at the onset of vitrectomy from 20 diabetic patients with PDR and 20 nondiabetic control subjects with nonproliferative ocular disease. Both groups were matched by serum levels of VCAM-1 and VEGF. VCAM-1 and VEGF were determined by enzyme-linked immunosorbent assay. Statistics were determined using the Mann-Whitney U test and Spearman's rank correlation test.RESULTS -The intravitreous concentration of VCAM-1 was significantly elevated in diabetic patients with PDR compared with control subjects (26 ng/ml [19 -118] vs. 22 ng/ml [20 -47], P Ͻ 0.05). A direct correlation between VCAM-1 and total vitreous proteins was detected in diabetic patients (r ϭ 0.64, P ϭ 0.003), but not in control subjects. After adjusting for total intravitreous proteins, VCAM-1 was significantly lower in diabetic patients with PDR than in control subjects (8.2 ng/ml [4 -31.4] vs. 43.1 ng/ml [9.7-100], P Ͻ 0.001). Intravitreous VEGF concentrations were higher in patients with PDR than in control subjects in absolute terms (1.34 ng/ml [0.16 -6.22] vs. 0.009 ng/ml [0.009 -0.044], P Ͻ 0.0001) and after correcting for total vitreal proteins (0.33 ng/ml [0.01-2.3] vs. 0.013 ng/ml [0.003-0.035], P ϭ 0.0001). Finally, the vitreous ratio of VCAM-1 to proteins correlated with the vitreous ratio of VEGF to proteins in both diabetic patients (r ϭ 0.74, P ϭ 0.001) and control subjects (r ϭ 0.84, P ϭ 0.005).CONCLUSIONS -The low proportion of VCAM-1 in relation to total vitreal proteins observed in diabetic patients with PDR suggests that VCAM-1 is quenched by diabetic retina. In addition, the direct correlation detected between VCAM-1 and VEGF suggests that cellular adhesion and neovascularization may be linked processes.
Diabetes Care 24:516 -521, 2001P roliferative diabetic retinopathy (PDR) is characterized by extensive neovascularization and vessel intrusion into the vitreous body, with subsequent bleeding and scarring surrounding new vessels, leading to severe visual impairment. Ischemic areas of the retina seem to be essential stimuli for the angiogenic process mediated by specific growth factors. This includes the expression of vascular endothelial growth factor (VEGF) by retinal glial cells (1) and vascular endothelial cells (2). It is thought that capillary occlusion by increased adhesion of leukocytes and macrophages to the endothelium has a crucial role in the process of retinal ischemia (3). In addition, monocytes exposed to glycated collagen show increased adhesiveness (4), and several studies indicate that circulating leukocytes are activated in diabetic patients (5,6).Vascular cell adhesion molecule (VCAM)-1, a member of the immunoglobulin supergene family of cellular adhesion molecules, is involved in the re...