Elevated plasma CD105 and vitreous VEGF levels in diabetic retinopathy

Abstract

Diabetic retinopathy is the major cause of premature blindness amongst adults in the western world [1].Characterised by microvascular occlusion and leakage due to endothelial and pericyte cell damage and basement membrane thickening, macular oedema, neovascularisation and vitreous haemorrhage can eventually result in blindness [1]. Sustained hyperglycaemia results in retinal under perfusion, hypoxia and retinal ischaemia. These changes induce the production of AbstractDiabetic retinopathy is the leading cause of blindness in the industrialized world. Hyperglycaemia induces retinal hypoxia that upregulates a range of vasoactive factors which may lead to macular oedema and/or angiogenesis and hence potentially sight threatening retinopathy. In this study, we have focused on the association of CD105 and vascular endothelial growth factor (VEGF) with the development and progression of diabetic retinopathy by means of quantifying their expression in the plasma and vitreous of diabetic patients. CD105 levels were quantified in the plasma of 38 type I diabetic patients at various stages of retinopathy and 15 non-diabetic controls. In an additional cohort of 11 patients with advanced proliferative retinopathy and 23 control subjects, CD105 and VEGF were measured in the vitreous. The values were expressed as median (range) and statistical analysis was carried out using the non-parametric Mann-Whitney U test. Plasma CD105 levels were significantly increased in diabetic patients [1.8 (1.1-2.4) ng/ml] compared with non-diabetic controls [0.7 (0.3-1.8) ng/ml] (p<0.01). Plasma CD105 levels were elevated in diabetic patients with all stages of retinopathy, the highest level was observed in background retinopathy [2.3 (2.1-2.5) ng/ml] followed by proliferative retinopathy [2.1 (0.9-2.8) ng/ml] and advanced proliferative retinopathy [1.4 (0.6-1.8) ng/ml]. Vitreous contents of CD105 did not differ between controls and patients with advanced proliferative retinopathy, but vitreous levels of VEGF were elevated by ~3-fold in patients with advanced proliferative retinopathy [7.2 (1.90-15.60) ng/ml] compared with the control subjects [1.80 (1.10-2.210)] (p<0.01). These observations indicate that plasma levels of CD105 and vitreous levels of VEGF are associated with diabetic retinopathy, suggesting that CD105 and the angiogenic factor VEGF may play a critical role in the development and progression of diabetic retinopathy. Further studies are required to determine whether circulating CD105 levels could serve as a surrogate marker for early stage retinopathy and for monitoring disease progression.

Developmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung

“…Exaggerated VEGF production has been proposed to play an important role in the pathogenesis of a wide variety of diseases, including tumor neovascularization, asthma, pulmonary edema, atherosclerosis, and the retinopathies of the NB and the diabetic (5,9,51,(54)(55)(56)(57). The present studies suggest that the pathologic effects of VEGF in these disorders may be controlled by interventions that control NO production.…”

Multiple Variants in Vascular Endothelial Growth Factor (VEGFA) Are Risk Factors for Time to Severe Retinopathy in Type 1 Diabetes

“…VEGFA is significantly upregulated in diabetic retinopathy, particularly in retinal pigmented epithelial cells, glial cells, and vitreal fibroblasts (20). Moreover, higher plasma (21) and vitreous VEGFA (21-23) levels were found in individuals with proliferative diabetic retinopathy (PDR) when compared with nondiabetic control subjects (21) or with individuals with nonocular diseases (22). Phase II clinical trials have shown safety and efficacy of intraocular injections of pegaptanib, an anti-VEGFA aptamer in the treatment of diabetic macular edema (24).…”

Adherence to diabetic eye examination guidelines in Australia: the National Eye Health Survey

“…VEGF, a multifunctional cytokine expressed and secreted by many cells, induces angiogenesis and strongly increases vascular permeability 194 . It alters the blood-retinal barrier 195 and is increased in the vitreous of eyes with PDR [196][197][198] . A role for PDGF ligands and receptors has been postulated in the pathogenesis of different proliferative diseases, including PDR 199 .…”