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BACKGROUND The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown. METHODS At 89 clinical sites, we randomly assigned 660 adults (mean age, 61±10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0(More)
PURPOSE Hepatocyte growth factor (HGF), also called scatter factor, stimulates growth and motility in nonocular endothelial cells and smooth muscle cells through its receptor c-Met. Recent reports suggest that HGF is increased in the serum and vitreous of patients with proliferative diabetic retinopathy and that smooth muscle cells and retinal pigment(More)
PURPOSE To determine the effect of pigment epithelium-derived factor (PEDF) in a mouse model of ischemia-induced retinal neovascularization and on vascular endothelial growth factor (VEGF)--induced migration and growth of cultured microvascular endothelial cells. METHODS Human recombinant PEDF was expressed in the human embryonic kidney 293 cell line and(More)
Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen which mediates its effects by binding to tyrosine kinase receptors. We have characterized the VEGF-activated intracellular signal transduction pathway in bovine aortic endothelial cells and correlated this to its mitogenic effects. VEGF induced concentration- and time-dependent(More)
PURPOSE Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic factor that serves an important role in numerous ischemic retinopathies. The authors studied the hypoxic gene regulation of two known VEGF receptors (KDR and Flt) and its mechanism in cultured bovine retinal endothelial cells (BREC). METHODS Confluent monolayers(More)
OBJECTIVE To evaluate the extent of pancreatic β-cell function in a large number of insulin-dependent diabetic patients with a disease duration of 50 years or longer (Medalists). RESEARCH DESIGN AND METHODS Characterization of clinical and biochemical parameters and β-cell function of 411 Medalists with correlation with postmortem morphologic findings of(More)
PURPOSE To determine the mechanistic role for adenosine and adenosine receptors in the hypoxic induction of vascular endothelial growth factor (VEGF) in retinal microvascular cells. METHODS Bovine retinal capillary endothelial cells and microvascular pericytes were studied under normoxic (95% air, 5% CO2) or hypoxic conditions (0% to 2% O2, 5% CO2, 93% to(More)
PURPOSE A critical early event in the pathogenesis of diabetic retinopathy is leukocyte adhesion to the diabetic retinal vasculature. The process is mediated, in part, by intercellular adhesion molecule-1 (ICAM-1) and results in blood-retinal barrier breakdown and capillary nonperfusion. This study evaluated the expression and function of the corresponding(More)
OBJECTIVE To assess complication prevalence and identify protective factors in patients with diabetes duration of ≥50 years. Characterization of a complication-free subgroup in this cohort would suggest that some individuals are protected from diabetes complications and allow identification of endogenous protective factors. RESEARCH DESIGN AND METHODS(More)