title: Altered vascular microenvironment by bevacizumab in diabetic fibrovascular membrane.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the impact of intravitreal bevacizumab (IVB) on three cellular components (vascular endothelial cells, pericytes, and myofibroblasts) of the vascular microenvironment in fibrovascular membranes (FVMs) of patients with proliferative diabetic retinopathy.
  
  
  METHODS
  Immunohistological studies with antibodies of CD34, αSMA, and transforming growth factor-β were performed on 20 surgical specimens obtained during a pars plana vitrectomy from 8 IVB-treated eyes, whereas 12 remained untreated. Four different indexes of vascular phenotype (vascular area, vascular major axis, CD34 endothelial area, and blood vessel density) and αSMA expression in vascular and stromal components were quantitatively analyzed.
  
  
  RESULTS
  The intraluminal area of blood vessels, CD34 endothelial area, and the blood vessel density in IVB-treated FVMs were significantly less than in untreated FVMs. The number of CD34 blood vessels in IVB-treated FVMs was similar to that in untreated FVMs. Intravitreal bevacizumab could not affect vascular and stromal αSMA area significantly. However, the ratio of vascular αSMA area/CD34 area was significantly higher in IVB-treated FVMs than in untreated FVMs. Transforming growth factor-β expression could be observed in the IVB-treated FVM.
  
  
  CONCLUSIONS
  Intravitreal bevacizumab might primarily affect blood vessels, and the effects on pericytes and myofibroblasts might be secondary. Intravitreal bevacizumab treatment regulates vascular microenvironment by the contraction of blood vessels, the increasing pericyte ratio, and transforming growth factor-β expression in FVMs of patients with proliferative diabetic retinopathy.
authors.affiliation: Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. snakao@med.kyushu-u.ac.jp
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nakao
authors.forename: Keijiro
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yoshida
authors.forename: Ri-Ichiro
authors.initials: R
authors.lastname: Kohno
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Enaida
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kono
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000068258:Bevacizumab; D060833:Cellular Microenvironment / Q000187:drug effects*; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000187:drug effects; D020286:Pericytes / Q000187:drug effects; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D053773:Transforming Growth Factor beta1; D000068258:Bevacizumab