Vitreous Levels of Vascular Cell Adhesion Molecule and Vascular Endothelial Growth Factor in Patients With Proliferative Diabetic Retinopathy

Abstract

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...

Proteome Analysis of Human Vitreous Proteins

“…We detected hundreds of spots at a time on a single gel in vitreous samples. Previous reports of the protein content of diseased vitreous using the conventional ELISA method have identified only one or several proteins from vitreous samples (1)(2)(3)(4)(5)(6)(7)(8)(9), because the amount of available vitreous was limited compared with other body fluids such as serum, cerebrospinal fluid, and urine. Proteome analysis method can overcome this drawback because the whole-vitreous protein profile can be presented on a single gel.…”

“…According to previous reports, various factors, including many kinds of proteins, are involved in the pathological processes of diabetic retinopathy. A breakdown of the bloodretina barrier is caused by an intraocular increase of vascular endothelial growth factor (VEGF) 1 (1-7), interleukin-6, angiotensin II, and many other cytokines and/or growth factors. New vessel formation is a very complex multistep process and is regulated by many proteins including cytokines and/or growth factors.…”

E-selectin-inducing activity in plasma from type 2 diabetic patients with maculopathy

“…Increased levels of adhesion molecules have been found in the vitreous of patients with proliferative diabetic retinopathy (10,14). However, only a few studies have examined the connection between expression of endothelial adhesion molecules and the development and progression of diabetic retinopathy.…”

Ocular Anti-VEGF Therapy for Diabetic Retinopathy: The Role of VEGF in the Pathogenesis of Diabetic Retinopathy

“…Another mechanism by which VEGF could promote angiogenesis is through the enhancement of intercellular adhesion molecule 1 (ICAM-1) (27) and vascular adhesion molecule 1 (VCAM-1) (39). In this regard, a direct correlation between VCAM-1 and VEGF in the vitreous fluid of diabetic patients with PDR has been reported (40).…”