title: Apelin in epiretinal fibrovascular membranes of patients with retinopathy of prematurity and the changes after intravitreal bevacizumab.
abstract: OBJECTIVE
  Apelin, a novel cytokine, was reported to regulate angiogenesis. The aim of this study was to investigate the correlation between apelin and retinopathy of prematurity (ROP), between apelin and the other known angiogenic cytokines including vascular endothelial growth factor (VEGF) and hypoxia-induced factor-1a (HIF-1a).
  
  
  METHODS
  The study included 36 ROP patients who underwent vitrectomy. Previous intravitreal bevacizumab (IVB) was performed in 18 patients (IVB group). The other ROP eyes belonged to non-IVB group. Surgical removed membranes from 10 patients who underwent vitrectomy for idiopathic preretinal membranes or macular hole served as control. The expression of apelin and angiotensin-1-like receptor (APJ) in the excised membranes was examined by fluorescence immunostaining. Quantitative reverse transcription polymerase chain reaction was used to examine the expression of apelin, VEGF, and HIF-1a mRNA.
  
  
  RESULTS
  The density of neovascularization in fibrovascular membranes was significantly correlated with the age and postconception age of ROP patients (r = -0.94, P < 0.01; r = -0.83, P = 0.04). In the non-IVB group, colocalization of the endothelial marker CD31 with the marker for apelin and colocalization of CD31 and APJ were observed. In the IVB group, staining of apelin and APJ were positive, whereas the staining of CD31 was negative. Expression of apelin mRNA, HIF-1a mRNA, and VEGF mRNA were significantly higher in ROP membranes than idiopathic epiretinal membranes. Expression of apelin mRNA and VEGF mRNA significantly correlate with HIF-1a mRNA (r = 0.64, P = 0.04; and r = 0.96, P < 0.01, respectively), but the expression of apelin mRNA did not significantly correlate with VEGF mRNA (r = 0.491, P = 0.15).
  
  
  CONCLUSIONS
  The apelin/APJ system may be involved in the development of retinal neovascularization of ROP. The present results showed that the effect of apelin was related to HIF-1a but independent with VEGF.
authors.affiliation: Department of Ophthalmology, People's Hospital, Peking University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan-rong
authors.initials: YR
authors.lastname: Jiang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lu
authors.forename: Hong
authors.initials: H
authors.lastname: Yin
authors.forename: Yong
authors.initials: Y
authors.lastname: Tao
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000073861:Apelin; D000075244:Apelin Receptors; D000068258:Bevacizumab; D019773:Epiretinal Membrane / Q000378:metabolism* / Q000601:surgery; D019084:Fluorescent Antibody Technique, Indirect; D005865:Gestational Age; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D058449:Intravitreal Injections; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015861:Retinal Neovascularization / Q000188:drug therapy / Q000378:metabolism*; D012178:Retinopathy of Prematurity / Q000145:classification / Q000188:drug therapy / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics; D014821:Vitrectomy
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000073861:Apelin; D000075244:Apelin Receptors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab