title: Colocalization of Tie2, angiopoietin 2 and vascular endothelial growth factor in fibrovascular membrane from patients with retinopathy of prematurity.
abstract: OBJECTIVE
  The tyrosine kinase receptor Tie2 and its ligands, the angiopoietins (Angs), play important roles in vascular integrity and neovascularization, modulating vascular endothelial growth factor (VEGF) activity. To elucidate the potential role of Angs and the Tie2 system in retinopathy of prematurity (ROP), we have investigated the expression of Angs, Tie2 and VEGF within fibroproliferative membranes in ROP.
  
  
  METHODS
  Fibroproliferative membranes were obtained from 38 cases with stage 5 ROP at the time of vitrectomy. Membranes were fixed in formalin and embedded in paraffin. Each specimen was serially sectioned for immunohistochemistry. Polyclonal antibodies specific for Ang1, Ang2, Tie2 and VEGF were used for immunostaining. Immunoreactivity for von Willebrand factor (factor VIII) was also assessed to confirm the identity of vascular endothelial cells.
  
  
  RESULTS
  Positive staining for Tie2 was observed in 23 of 38 specimens (60.5%). Tie2 was localized in vascularized regions of fibrovascular membranes and was co- expressed with VEGF and factor VIII. Ang2 stained positively in 18 of 38 (47.3%) serial sections where Tie2 was present, and was also co-expressed with VEGF and factor VIII. Ang1 was not generally observed in these specimens (3/38).
  
  
  CONCLUSIONS
  VEGF and Ang2-Tie2 interactions may play an important role in the pathogenesis of ROP.
authors.affiliation: Department of Ophthalmology, Fukuoka University, School of Medicine, Fukuoka, Japan. nao_u@nifty.com
authors.forename: Naoyasu
authors.initials: N
authors.lastname: Umeda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ozaki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyajima-Uchida
authors.forename: Kenji
authors.initials: K
authors.lastname: Oshima
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D042702:Angiopoietin-2; D001724:Birth Weight; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D005355:Fibrosis; D019084:Fluorescent Antibody Technique, Indirect; D005865:Gestational Age; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008566:Membranes; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D042787:Receptor, TIE-2; D012160:Retina / Q000378:metabolism / Q000473:pathology; D015861:Retinal Neovascularization / Q000378:metabolism*; D012178:Retinopathy of Prematurity / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D042702:Angiopoietin-2; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2