title: Time-lapse imaging of retinal angiogenesis reveals decreased development and progression of neovascular sprouting by anecortave desacetate.
abstract: OBJECTIVE
  To elucidate the effects of anecortave desacetate (AD) treatment on the kinetics of neovascular sprouting and its molecular mechanisms in retinal explants and during retinal vascular development in mice.
  
  
  METHODS
  The antiangiogenic effects of AD on retinal angiogenesis were evaluated using two different models: a retinal explant model treated with vascular endothelial growth factor (VEGF) and a mouse model of postnatal retinal vascular development. Time-sequential observation was followed by the quantification of movements in neovascular sprouts and microglia. Real time-PCR was performed for the measurement of mRNA levels.
  
  
  RESULTS
  AD treatment significantly reduced the number of neovascular sprouts in retinal explants in a dose-dependent manner. Time-lapse imaging demonstrated that AD suppressed the new development and elongation of neovascular sprouts and the motility of tip cells. Moreover, AD treatment disturbed the filopodial extension and significantly decreased the transcriptional levels of KDR and platelet-derived growth factor-B, which are highly expressed in tip cells. In addition, it was confirmed that AD inhibited postnatal development of the retinal vasculature in mice, including filopodial extension in tip cells. These data suggest that AD suppresses both the development and the progression of sprouting angiogenesis. Interestingly, VEGF-induced microglial movements were also reduced in the retinal explants treated with AD. These changes were consistent with decreased mRNA levels of SDF-1 and Flt-1, which regulate the activation of inflammatory cells.
  
  
  CONCLUSIONS
  AD inhibited both the development and the progression of VEGF-induced retinal angiogenesis mediated, in part, by the suppression of tip cell motility in two angiogenic models.
authors: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo, Kyoto, Japan.
authors: Noriyuki
authors: N
authors: Unoki
authors: Tomoaki
authors: T
authors: Murakami
authors: Ken
authors: K
authors: Ogino
authors: Masayuki
authors: M
authors: Nukada
authors: Nagahisa
authors: N
authors: Yoshimura
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019084:Fluorescent Antibody Technique, Indirect; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009924:Organ Culture Techniques; D011244:Pregnadienediols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015861:Retinal Neovascularization / Q000378:metabolism / Q000517:prevention & control*; D012171:Retinal Vessels / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000633:toxicity; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D011244:Pregnadienediols; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; C418047:anecortave acetate