title: Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice.
abstract: The present study was designed to evaluate the effects of doxazosin on experimental choroidal neovascularization (CNV) in mice.
  
  
  
  Six- to 8-week-old male C57BL/6 mice were divided into a control group and a doxazosin-treated group (5 mg/kg, i.p., daily). Experimental CNV was induced by laser photocoagulation. Seven and 14 days after laser induction, fluorescein angiography, choroidal flat mounts, and histological studies were performed to evaluate the fluorescence leakage, area, and thickness of CNV lesions, respectively. In addition, western blot analysis was carried out to assess the inhibitory effects of doxazosin on the PI3K/Akt/mTOR signaling pathway and the expression levels of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), which are involved in CNV model.
  
  
  
  Compared with the control group, the doxazosin-treated group demonstrated significantly less fluorescence leakage on day 7 and 14 after laser induction. Both the area and the thickness of CNV lesions in the doxazosin-treated group were significantly decreased. Mechanistically, PI3K/Akt/mTOR signaling pathway activation was significantly suppressed in the doxazosin-treated group. The expression of HIF-1α and VEGF was also notably reduced by systemic doxazosin treatment.
  
  
  
  Doxazosin exerts antiangiogenic actions in an experimental mouse model of CNV and may be a potential adjunctive therapy for neovascular age-related macular degeneration in humans.
authors.affiliation: 1 Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China .|2 Shanghai Key Laboratory of Ocular Fundus Diseases , Shanghai, China .
authors.forename: Jiaxian
authors.initials: J
authors.lastname: Guo
authors.affiliation: 1 Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China .|2 Shanghai Key Laboratory of Ocular Fundus Diseases , Shanghai, China .
authors.forename: Xueting
authors.initials: X
authors.lastname: Luo
authors.affiliation: 1 Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China .|2 Shanghai Key Laboratory of Ocular Fundus Diseases , Shanghai, China .
authors.forename: Jian
authors.initials: J
authors.lastname: Liang
authors.affiliation: 1 Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China .|2 Shanghai Key Laboratory of Ocular Fundus Diseases , Shanghai, China .
authors.forename: Meichun
authors.initials: M
authors.lastname: Xiao
authors.affiliation: 1 Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, China .|2 Shanghai Key Laboratory of Ocular Fundus Diseases , Shanghai, China .
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D017292:Doxazosin / Q000008:administration & dosage / Q000494:pharmacology*; D007834:Lasers; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D020533:Angiogenesis Inhibitors; D017292:Doxazosin
keywords: antiangiogenic; choroidal neovascularization; doxazosin; laser-induced