title: A potential therapeutic strategy for inhibition of ocular neovascularization with a new endogenous protein: rhEDI-8t.
abstract: BACKGROUND
  Endogenous angiogenesis inhibitors act as natural negative feedback in the focal area during the neovascularization process, and have less interference on physiological angiogenesis, and thus fewer negative side-effects. These inhibitors are potential candidates to combine with or substitutes for current popular anti-angiogenesis treatments to have synergistic effect. In this study, the effects of recombinant endothelial growth inhibitor protein (rhEDI-8t), a novel endogenous protein originated from collagen VIII, was investigated on ocular neovascularization (NV). Endostatin, a well-identified endogenous angiogenesis inhibitor, was compared in parallel and served as a positive control.
  
  
  METHODS
  The inhibitory effect of rhEDI-8t on vascular endothelial cells was evaluated by a human umbilical vascular endothelial cells (HUVEC) proliferation test and a bovine aortic endothelial cells (BAEC) migration experiment. The effect of rhEDI-8t on ocular NV was further investigated in mice with choroidal neovascularization (choroidal NV) induced by laser, ischemic retinopathy and transgenic mice with expression of VEGF in photoreceptors (rho/VEGF) respectively.
  
  
  RESULTS
  RhEDI-8t inhibited the growth of HUVECs and migration of BAECs stimulated by basic fibroblast growth factor (bFGF). Mice intravitreally treated with rhEDI-8t showed a significant reduction of choroidal NV, retinal NV and subretinal NV.
  
  
  CONCLUSIONS
  Endogenous angiogenesis inhibitor rhEDI-8t showed a potent anti-angiogenesis effect in both in vitro and in vivo experiments. It contributed to the suppression of ocular NV. The study suggested that rhEDI-8t could be a subsidiary potent therapeutic medicine in addition to anti-VEGF therapy in future clinical anti-angiogenesis treatment.
authors: The Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197, Ruijin Er Road, Shanghai, China.
authors: Ling
authors: L
authors: Zhang
authors: Xi
authors: X
authors: Shen
authors: Qing
authors: Q
authors: Lu
authors: Qingwei
authors: Q
authors: Zhou
authors: Jiaqi
authors: J
authors: Gu
authors: Renbao
authors: R
authors: Gan
authors: Hui
authors: H
authors: Zhang
authors: Xiaodong
authors: X
authors: Sun
authors: Bing
authors: B
authors: Xie
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000473:pathology / Q000517:prevention & control*; D024102:Collagen Type VIII / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D043169:Endostatins / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D058449:Intravitreal Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins; D015861:Retinal Neovascularization / Q000473:pathology / Q000517:prevention & control*; D013047:Specific Pathogen-Free Organisms; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D024102:Collagen Type VIII; D043169:Endostatins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C573123:rhEDI-8t protein, human; C467480:vascular endothelial growth factor A, mouse; D016222:Fibroblast Growth Factor 2