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The vascular endothelial growth factor (VEGF) family of growth factors controls pathological angiogenesis and increased vascular permeability in important eye diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). The purpose of this review is to develop new insights into the cell biology of VEGFs and vascular cells in(More)
BACKGROUND In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) cause blindness by neovascularization and subsequent fibrosis, but their relative contribution to both processes is unknown. We hypothesize that the balance between levels of pro-angiogenic VEGF and pro-fibrotic CTGF(More)
Ocular diseases dominated by neovascularization, such as age-related macular degeneration (AMD), retinal vein occlusions, and diabetic retinopathy (DR), often culminate in severe visual loss and ultimately blindness. In most of these conditions, ischemic retinal areas produce abnormal amounts of angiogenic growth factors that induce excessive angiogenesis,(More)
Breakdown of the inner endothelial blood-retinal barrier (BRB), as occurs in diabetic retinopathy, age-related macular degeneration, retinal vein occlusions, uveitis and other chronic retinal diseases, results in vasogenic edema and neural tissue damage, causing loss of vision. The central mechanism of altered BRB function is a change in the permeability(More)
Purpose. An early hallmark of preclinical diabetic retinopathy is thickening of the capillary basal lamina (BL). TGF-beta, a multipotent cytokine acting through its receptors ALK5 and -1, has been postulated to be involved in this phenomenon. In light of this possible role, TGF-beta signaling and its downstream molecular effects were characterized in(More)
The functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study,(More)
PURPOSE Vascular endothelial growth factor-A (VEGF) causes increased vascular permeability and leukocyte adhesion in preclinical diabetic retinopathy (PCDR). Another hallmark of PCDR is thickening of the capillary basement membrane (BM). Recently, VEGF has been shown to induce expression of profibrotic genes such as transforming growth factor (TGF)-beta1(More)
INTRODUCTION In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) may cause blindness by neovascularisation followed by fibrosis of the retina. It has previously been shown that a shift in the balance between levels of CTGF and VEGF in the eye is associated with this angiofibrotic(More)
Activated protein C (APC) has both anticoagulant activity and direct cell-signaling properties. APC has been reported to promote cancer cell migration/invasion and to inhibit apoptosis and therefore may exacerbate metastasis. Opposing these activities, APC signaling protects the vascular endothelial barrier through sphingosine-1-phosphate receptor-1(More)
OBJECTIVE Increased levels of vascular endothelial growth factor (VEGF) in human plasma samples have suggested that circulating VEGF is a cause of endothelial dysfunction in diabetes mellitus. However, artificial release of VEGF from platelets as a source of VEGF in plasma samples, as also occurs in serum samples, has not been ruled out in these studies. (More)