Sean Francis Hackett

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VEGF and Angiopoietin-1 requisitely collaborate during blood vessel development. While Angiopoietin-1 obligately activates its Tie2 receptor, Angiopoietin-2 can activate Tie2 on some cells, while it blocks Tie2 activation on others. Our analysis of mice lacking Angiopoietin-2 reveals that Angiopoietin-2 is dispensable for embryonic vascular development but(More)
Understanding molecular mechanisms regulating angiogenesis may lead to novel therapies for ischemic disorders. Hypoxia-inducible factor 1 (HIF-1) activates vascular endothelial growth factor (VEGF) gene expression in hypoxic/ischemic tissue. In this study we demonstrate that exposure of primary cultures of cardiac and vascular cells to hypoxia or AdCA5, an(More)
In this study, we used ischemia-induced retinal neovascularization (NV) as a model to investigate the possible role of microRNAs in a clinically important disease process. Microarray analysis demonstrated seven microRNAs (miR-106a, -146, -181, -199a, -214, -424, and -451) that were substantially increased and three microRNAs (miR-31, -150, and -184) that(More)
Vascular endothelial growth factor (VEGF) has been implicated in retinal neovascularization (NV), but it has been difficult to produce retinal NV with exogenous VEGF. We investigated the effect of increased VEGF expression in the retina using tissue-specific, gain-of-function transgenic mice in which the bovine rhodopsin promoter is coupled to the gene for(More)
PURPOSE Hypoxia inducible factor-1 (HIF-1) is a transcription factor composed of HIF-1alpha and HIF-1beta subunits. HIF-1 transactivates multiple genes whose products play key roles in oxygen homeostasis, including vascular endothelial growth factor (VEGF). This study was designed to determine whether HIF-1 levels are increased in ischemic retina and(More)
Vascular development in the embryo requires coordinated signaling through several endothelial cell-specific receptors; however, it is not known whether this is also required later during retinal vascular development or as part of retinal neovascularization in adults. The Tie2 receptor has been implicated in stabilization and maturation of vessels through(More)
In this study, we used small interfering RNA (siRNA) directed against vascular endothelial growth factor receptor 1 (vegfr1) mRNA to investigate the role of VEGFR1 in ocular neovascularization (NV). After evaluating many siRNAs, Sirna-027 was identified; it cleaved vegfr1 mRNA at the predicted site and reduced its levels in cultured endothelial cells and in(More)
There are no effective treatments for inherited retinal degenerations, which are prevalent causes of visual disability. Several proteins promote the survival of various types of neurons, and increasing expression of one or more of these survival factors is a promising strategy for a new treatment. Studies examining the effects of intravitreous injections of(More)
Age-related macular degeneration (AMD), the leading cause of severe vision loss in the elderly, is a complex disease that results from genetic modifications that increase susceptibility to environmental exposures. Smoking, a major source of oxidative stress, increases the incidence and severity of AMD, and antioxidants slow progression, suggesting that(More)
PURPOSE Platelet-derived growth factor (PDGF) has been implicated in vascular proliferative retinopathies, such as diabetic retinopathy, and in nonvascular retinopathies, such as proliferative vitreoretinopathy. Traction retinal detachment is a central feature of both types of disease. Hemizygous rhodopsin promoter/PDGF-B (rho/PDGF-B) transgenic mice(More)