A5033007288- Angiogenesis and VEGF in Cancer
- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
- Retinal Development and Disorders
- Axon Guidance and Neuronal Signaling
- Coronary Interventions and Diagnostics
- Cell Adhesion Molecules Research
- Retinal and Optic Conditions
- Cancer, Hypoxia, and Metabolism
- Retinopathy of Prematurity Studies
- Ocular Diseases and Behçet’s Syndrome
- Zebrafish Biomedical Research Applications
- Biomarkers in Disease Mechanisms
- Congenital heart defects research
- Proteoglycans and glycosaminoglycans research
- Cancer-related Molecular Pathways
- Chronic Kidney Disease and Diabetes
- Neurological Disorders and Treatments
- interferon and immune responses
- Retinal Imaging and Analysis
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Neonatal Respiratory Health Research
- Renin-Angiotensin System Studies
- Tissue Engineering and Regenerative Medicine
Smith-Kettlewell Eye Research Institute
2015-2024
Harvard University
2004-2024
Massachusetts Eye and Ear Infirmary
2004-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2024
London Eye Hospital
2024
Newcastle upon Tyne Hospitals NHS Foundation Trust
2019
Wellcome Centre for Mitochondrial Research
2019
Newcastle University
2019
University of North Carolina at Chapel Hill
1999-2019
University College London
2003-2016
The murine VEGF gene is alternatively transcribed to yield the VEGF120, VEGF164, and VEGF188 isoforms, which differ in their potential bind heparan sulfate neuropilin-1 stimulate endothelial growth. Here, role retinal vascular development was studied mice selectively expressing single isoforms. VEGF164/164 were normal, healthy, had normal angiogenesis. In contrast, VEGF120/120 exhibited severe defects outgrowth patterning, whereas VEGF188/188 displayed venular but impaired arterial...
Angiogenesis is an essential component of skeletal development and VEGF signaling plays important if not pivotal role in this process. Previous attempts to examine the roles vivo have been largely unsuccessful because deletion even one allele leads embryonic lethality before initiated. The availability mice expressing only VEGF120 isoform (which do survive term) has offered opportunity explore function during development. Our study these provides new evidence for multiple both endochondral...
Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological neovascularization. In the current paper, mechanisms of neovascularization are compared contrasted. During neovascularization, absolute relative expression levels for VEGF164 increased to a greater degree than during Furthermore, extensive leukocyte adhesion was observed at leading edge pathological, but not physiological, When VEGF164-specific neutralizing aptamer administered, it potently...
Vascular endothelial growth factor (VEGF), a that is critical for development of the vascular system in mouse embryos, exists as at least three isoforms, VEGF120, VEGF164, and VEGF188. The isoforms have different affinities heparan sulfate well known VEGF receptors, VEGFR-1 (Flt-1), VEGFR-2 (Flk-1), neuropilin-1, suggesting may play distinct roles development. To determine whether there are differences organ-specific expression patterns would support this concept, we used quantitative RNase...
The murine VEGF gene is alternatively transcribed to yield the VEGF120, VEGF164, and VEGF188 isoforms, which differ in their potential bind heparan sulfate neuropilin-1 stimulate endothelial growth. Here, role retinal vascular development was studied mice selectively expressing single isoforms. VEGF164/164 were normal, healthy, had normal angiogenesis. In contrast, VEGF120/120 exhibited severe defects outgrowth patterning, whereas VEGF188/188 displayed venular but impaired arterial...
We describe the genomic organization and functional characterization of mouse gene encoding vascular endothelial growth factor (VEGF), a polypeptide implicated in embryonic development postnatal angiogenesis. The coding region for VEGF is interrupted by seven introns encompasses approximately 14 kilobases. Organization exons suggests that, similar to human gene, alternative splicing generates 120-, 164-, 188-amino acid isoforms, but does not predict fourth isoform corresponding VEGF206....
Aptamers recognize their targets with extraordinary affinity and specificity. The aptamer-based therapeutic, Macugen, is derived from a modified 2′fluoro pyrimidine RNA inhibitor to vascular endothelial growth factor (VEGF) now being used treat the wet form of age-related macular degeneration. This VEGF 165 aptamer binds specifically isoform, dimeric protein receptor-binding domain heparin-binding (HBD). To understand molecular recognition between this aptamer, binding experiments were show...
Vascular endothelial growth factor A (VEGF-A) is a validated therapeutic target in several angiogenic- and vascular permeability-related pathological conditions, including certain cancers potentially blinding diseases, such as age-related macular degeneration diabetic retinopathy. We others have shown that VEGF-A also plays an important role neuronal development neuroprotection, the neural retina. Antagonism of function might therefore present risk to survival significant adverse effect....
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Retinal ganglion cell (RGC) loss occurs in response to increased intraocular pressure (IOP) and/or retinal ischemia glaucoma and leads impairment of vision. This study was undertaken test the efficacy erythropoietin (EPO) providing neuroprotection RGCs vivo.The neuroprotective effects EPO were studied DBA/2J mouse model glaucoma. Mice intraperitoneally injected with control substances or various doses EPO, starting at age 6 months continuing for an additional 2, 4, months. labeled...
Angiogenesis is central to both normal and pathologic processes. Endothelial cells (ECs) express O-glycoproteins that are believed play important roles in vascular development stability. Endomucin-1 (EMCN) a type I O-glycosylated, sialic-rich glycoprotein, specifically expressed by venous capillary endothelium. Evidence has pointed potential role for EMCN angiogenesis but it had not been directly investigated. In this study, we examined the of modulating levels vivo vitro. Reduction led...
The longer splice isoforms of vascular endothelial growth factor-A (VEGF-A), including mouse VEGF164, contain a highly basic heparin-binding domain (HBD), which imparts the ability these to be deposited in heparan sulfate-rich extracellular matrix and interact with prototype sulfated glycosaminoglycan, heparin. shortest isoform, VEGF120, lacks this is freely diffusible upon secretion. Although HBD has been attributed significant relevance VEGF-A biology, molecular determinants site are...
Purpose.: Two noninvasive delivery strategies for VEGF/PDGF receptor tyrosine kinase inhibitors (RTKI) were explored that exploited uveal retention as a means establishing an ocular drug depot: single oral "loading" dose and topical administration. Methods.: Melanin binding was confirmed by centrifugation mass spectrometry. Ocular examined in pigmented albino rats. release kinetics measured 3 to 28 days postdosing Microautoradiography used demonstrate of RTKI the tract. A depot pazopanib...
Abstract The endothelial glycocalyx, located at the luminal surface of endothelium, plays an important role in regulation leukocyte adhesion, vascular permeability, and homeostasis. Endomucin (EMCN), a component is mucin-like transmembrane glycoprotein selectively expressed by venous capillary endothelium. We have previously shown that knockdown EMCN impairs retinal development vivo growth factor 165 isoform (VEGF165)-induced cell migration, proliferation, tube formation human cells vitro...
Fenestrae are small pores in the endothelium of renal glomerular, gastrointestinal, and endocrine gland capillaries involved bidirectional exchange molecules between blood tissues. Although decades studies have characterized fenestrae at ultrastructural level, little is known on mechanisms by which form. We present development an vitro assay rapid abundant fenestra induction enables a detailed study their biogenesis. Through use agents that stabilize or disassemble actin microfilaments, we...
The longer splice isoforms of VEGF (vascular endothelial growth factor)-A, including VEGF(164(165)), contain a highly basic HBD (heparin-binding domain). This domain allows these to interact with and localize the HS (heparan sulfate)-rich extracellular matrix, bind co-receptor Nrp-1 (neuropilin-1). Heparin-binding VEGF-A are critical for survival: mice engineered express exclusively non-heparin-binding VEGF(120) have diminished vascular branching during embryonic development die from...
Characterization of a mouse model spontaneous choroidal neovascularization (sCNV) and its effect on retinal architecture function.The sCNV phenotype was characterized by using fundus photography, fluorescein angiography, confocal scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), ERG, immunostaining, biochemistry, electron microscopy. A role for VEGF-A signaling in investigated neutralizing antibodies macrophages explored cell-depletion studies.The starts between...