title: Effects of apelin and vascular endothelial growth factor on central retinal vein occlusion in monkey eyes intravitreally injected with bevacizumab: a preliminary study.
abstract: OBJECTIVE
  To examine the intraocular distribution of bevacizumab at four weeks after intravitreal bevacizumab (IVB) injection and to investigate the effects of IVB on apelin and vascular endothelial growth factor (VEGF) in the central retinal vein occlusion (CRVO) of monkey eyes.
  
  
  METHODS
  Direct laser coagulation was performed on all branch retinal veins in the right eyes of six Rhesus monkeys to establish a CRVO model. The eyes of the first three monkeys were enucleated one week, two weeks, and 24 weeks after the establishment of the CRVO model; this was the CRVO group. Subsequently, IVB was injected into the eyes of the last three monkeys one week, two weeks, and 24 weeks after laser coagulation; this was the IVB group. The left eye of the first monkey was used as normal control. Immunohistochemistry and reverse-transcription PCR was used to examine the expression of apelin and VEGF. The penetration of bevacizumab into the retina and iris was investigated by fluorescence immunostaining.
  
  
  RESULTS
  Immunoreactivity for bevacizumab could be detected in the vessel walls of the iris and choroid on day 28 after injecting IVB: apelin and VEGF staining had been more prominent than normal in the CRVO eye, but these decreased following IVB injection. Expression of apelin mRNA (p<0.01) was lower in the IVB group than the CRVO group and did not vary significantly between groups.
  
  
  CONCLUSIONS
  Bevacizumab could be detected in the iris and choroid after four weeks of intravitreal injection. Apelin may be partially suppressed by bevacizumab, and it may play a role in retinal neovascularization during the development of CRVO.
authors.affiliation: Department of Ophthalmology, People's Hospital, Peking University, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lu
authors.forename: Yong
authors.initials: Y
authors.lastname: Tao
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Liang
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Jiang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000073861:Apelin; D000068258:Bevacizumab; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D058449:Intravitreal Injections; D017075:Laser Coagulation / Q000009:adverse effects; D008253:Macaca mulatta; D012333:RNA, Messenger / Q000032:analysis; D012169:Retinal Vein / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D012170:Retinal Vein Occlusion / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014822:Vitreous Body / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: C115436:APLN protein, human; D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000073861:Apelin; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab