title: Insulin-Like Growth Factor Binding Protein-Related Protein 1 Inhibit Retinal Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy.
abstract: To explore the inhibitory effect of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) on retinal angiogenesis and its underlying molecular mechanisms in the mouse model of oxygen-induced retinopathy (OIR).
  
  
  
  C57BL/6J mice were classified into three groups as control group, OIR nonintervention group, and OIR intervention group. Postnatal day 12 (P12) mice in OIR intervention group were received recombinant mouse IGFBP-rP1 (50, 100, and 200 ng/mL) intravitreal injection. Five days later, the proliferative neovascular responses were estimated by quantifying the new vessel areas in flattening retinal tissues stained by high molecular fluorescein isothiocyanate-dextran and counting the numbers of neovascular cell nuclei breaking through the internal limiting membrane in cross sections. Expressions of phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2), ERK1/2, and vascular endothelial growth factor (VEGF) proteins in retinal tissues were assessed by western blot analysis.
  
  
  
  Irregular neovascularization, nonperfusion region, and fluorescence leakage were observed in OIR models. The expression of retinal p-ERK1/2 and VEGF proteins were significantly upregulated in OIR nonintervention group compared with control group. The area ratio of retinal new vessels and the number of neovascular cell nuclei in OIR intervention group both decreased significantly, following the downregulation of retinal p-ERK1/2 protein expression and VEGF protein expression in a dose-dependent manner. Moreover, there was no significant difference in retinal ERK1/2 protein expression.
  
  
  
  IGFBP-rP1 inhibits retinal angiogenesis by blocking ERK signaling pathway and downregulating VEGF expression in the mouse model of OIR. It highlights the potential importance of IGFBP-rP1 serving as a target of gene therapy for retinal neovascularization in the future.
authors.affiliation: Department of Ophthalmology, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, China .
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, China .
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, China .
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Ophthalmology, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, China .
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, China .
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000008:administration & dosage / Q000633:toxicity*; D015861:Retinal Neovascularization / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1; D010100:Oxygen
keywords: ERK signaling pathway; angiogenesis; insulin-like growth factor binding protein-related protein 1; retina; vascular endothelial growth factor