Recombinant human VEGF165b inhibits experimental choroidal neovascularization

Autor: Christine Spee, Jing Hua, Steven J. Harper, Yan Qiu, Satoru Kase, Emma S. Rennel, David R. Hinton, Anette L. Magnussen, Amanda J. Churchill, Alexander H. R. Varey, David O. Bates, Sandeep Dhayade
Rok vydání: 2010
Předmět:
Male
Vascular Endothelial Growth Factor A
Endothelium
genetic structures
Angiogenesis
Angiogenesis Inhibitors
chemistry.chemical_compound
Mice
Cell Movement
Medicine
Animals
Humans
Fluorescein Angiography
Vascular Endothelial Growth Factor Receptor-1
Dose-Response Relationship
Drug
business.industry
Retinal Vessels
Kinase insert domain receptor
Articles
Macular degeneration
Surface Plasmon Resonance
medicine.disease
Vascular Endothelial Growth Factor Receptor-2
eye diseases
Choroidal Neovascularization
Recombinant Proteins
Vascular endothelial growth factor
Mice
Inbred C57BL
Vascular endothelial growth factor A
Disease Models
Animal
Choroidal neovascularization
medicine.anatomical_structure
chemistry
Immunology
Cancer research
sense organs
Endothelium
Vascular
medicine.symptom
business
Blood vessel
Zdroj: Investigative ophthalmologyvisual science. 51(8)
ISSN: 1552-5783
Popis: Vascular endothelial growth factor (VEGF-A) is the principal stimulator of angiogenesis in wet age-related macular degeneration (AMD). However, VEGF-A is generated by alternate splicing into two families, the proangiogenic VEGF-A(xxx) family and the antiangiogenic VEGF-A(xxx)b family. It is the proangiogenic family that is responsible for the blood vessel growth seen in AMD.To determine the role of antiangiogenic isoforms of VEGF-A as inhibitors of choroidal neovascularization, the authors used a model of laser-induced choroidal neovascularization in the mouse eye and investigated VEGF-A(165)b effects on endothelial cells and VEGFRs in vitro.VEGF-A(165)b inhibited VEGF-A(165)-mediated endothelial cell migration with a dose effect similar to that of ranibizumab and bevacizumab and 200-fold more potent than that of pegaptanib. VEGF-A(165)b bound both VEGFR1 and VEGFR2 with affinity similar to that of VEGF-A(165). After laser injury, mice were injected either intraocularly or subcutaneously with recombinant human VEGF-A(165)b. Intraocular injection of rhVEGF-A(165)b gave a pronounced dose-dependent inhibition of fluorescein leakage, with an IC(50) of 16 pg/eye, neovascularization (IC(50), 0.8 pg/eye), and lesion as assessed by histologic staining (IC(50), 8 pg/eye). Subcutaneous administration of 100 microg twice a week also inhibited fluorescein leakage and neovascularization and reduced lesion size.These results show that VEGF-A(165)b is a potent antiangiogenic agent in a mouse model of age-related macular degeneration and suggest that increasing the ratio of antiangiogenic-to-proangiogenic isoforms may be therapeutically effective in this condition.
Databáze: OpenAIRE
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