title: Transthyretin represses neovascularization in diabetic retinopathy.
abstract: The apoptosis of human umbilical vein endothelial cells has been reportedly induced by the protein transthyretin (TTR). In human ocular tissue, TTR is generally considered to be secreted mainly by retinal pigment epithelial cells (hRPECs); however, whether TTR affects the development of neovascularization in diabetic retinopathy (DR) remains unclear.
  
  
  
  Natural and simulated DR media were used to culture human retinal microvascular endothelial cells (hRECs). Hyperglycemia was simulated by increasing the glucose concentration from 5.5 mM up to 25 mM, while hypoxia was induced with 200 µM CoCl2. To understand the effects of TTR on hRECs, cell proliferation was investigated under natural and DR conditions. Overexpression of TTR, an in vitro wound-healing assay, and a tube formation assay were employed to study the repression of TTR on hRECs. Real-time fluorescence quantitative PCR (qRT-PCR) was used to study the mRNA levels of DR-related genes, such asTie2,VEGFR1,VEGFR2,Angpt1,andAngpt2.
  
  
  
  The proliferation of hRECs was significantly decreased in the simulated hyperglycemic and hypoxic DR environments. The cells were further repressed by added exogenous or endogenous TTR only under hyperglycemic conditions. The in vitro migration and tube formation processes of the hRECs were inhibited with TTR; furthermore, in the hyperglycemia and hyperglycemia/hypoxia environments, the levels ofTie2andAngpt1mRNA were enhanced with exogenous TTR, while those ofVEGFR1,VEGFR2,andAngpt1were repressed.
  
  
  
  In hyperglycemia, the proliferation, migration, and neovascularization of hRECs were significantly inhibited by TTR. The key genes for DR neovascularization, includingTie2,VEGFR1,VEGFR2,Angpt1,andAngpt2, were regulated by TTR. Under DR conditions, TTR significantly represses neovascularization by inhibiting the proliferation, migration and tube formation of hRECs.
authors.affiliation: Department of Ophthalmology, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Ophthalmology, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yao
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D009924:Organ Culture Techniques; D011228:Prealbumin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D015861:Retinal Neovascularization / Q000235:genetics / Q000378:metabolism*; D012171:Retinal Vessels / Q000502:physiology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D011228:Prealbumin; D012333:RNA, Messenger; C000588866:KDR protein, human; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D005947:Glucose