title: Inhibition of ocular neovascularization by a novel peptide derived from human placenta growth factor-1.
abstract: OBJECTIVE
  To evaluate the effect of ZY1, a novel 21-amino acid peptide from human placenta growth factor-1 (PlGF-1), against ocular neovascularization, and to study its possible toxicity to the retina and the underlying mechanism of antiangiogenic effect.
  
  
  METHODS
  MTS assays, a modified Boyden chamber and Matrigel(™) were used to evaluate the effect of ZY1 on the proliferation, migration and tube formation of RF/6A rhesus macaque choroid-retina endothelial cells induced by vascular endothelial growth factor (VEGF) in vitro. The antiangiogenic effect of ZY1 was also studied with corneal micropocket angiogenesis assays and oxygen-induced retinopathy (OIR) assays in mice. Electrophysiological tests and histological examinations were used to study the possible toxicity of ZY1 against mouse neuroretina. Competitive ELISA and Western blotting were performed to elucidate the underlying mechanism of ZY1.
  
  
  RESULTS
  ZY1 inhibited VEGF-induced RF/6A proliferation, migration and tube formation. It also inhibited ocular neovascularization when applied to the corneal micropocket angiogenesis assays and OIR assays in mice. Electrophysiological tests and histological examinations revealed no evident functional or morphologic abnormalities in mouse neuroretina after ZY1 injection. ZY1 competed for binding to VEGFR-1 against PlGF and VEGF and inhibited VEGFR-1/ERK/AKT activation.
  
  
  CONCLUSIONS
  It is concluded that the novel peptide ZY1 is an effective inhibitor of ocular pathologic angiogenesis and may provide a promising alternative for ocular antiangiogenic therapy.
authors.affiliation: Department of Ophthalmology, The First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.forename: Qing
authors.initials: Q
authors.lastname: Gu
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016510:Corneal Neovascularization / Q000517:prevention & control*; D004195:Disease Models, Animal; D004596:Electroretinography; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008253:Macaca mulatta; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010100:Oxygen / Q000633:toxicity; D010446:Peptide Fragments / Q000494:pharmacology* / Q000633:toxicity; D012160:Retina / Q000187:drug effects*; D015861:Retinal Neovascularization / Q000517:prevention & control*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D008565:Membrane Proteins; C098069:PIGF protein, human; D010446:Peptide Fragments; D040281:Vascular Endothelial Growth Factor Receptor-1; D051058:Oncogene Protein v-akt; D010100:Oxygen