title: Suppression of retinal neovascularization by lentivirus-mediated netrin-1 small hairpin RNA.
abstract: OBJECTIVE
  The function of netrin-1 in pathological angiogenesis and its role in retinal neovascularization were investigated in the retinas of oxygen-induced retinopathy (OIR) mice by inhibition of netrin-1.
  
  
  METHODS
  Expression of netrin-1 mRNA and protein in the retinas of OIR mice was analyzed by quantitative RT-PCR and immunoblotting. Inhibition of retinal neovascularization was achieved by lentivirus-mediated netrin-1 small hairpin RNA (shRNA) infection. Retinal neovascularization was examined by fluorescein angiography and quantification of preretinal neovascular nuclei in retinal sections.
  
  
  RESULTS
  Both mRNA and protein expression of netrin-1 were significantly upregulated in postnatal day 17 OIR mouse retinas. Treatment of OIR mice with specific lentivirus-mediated netrin-1 shRNA dramatically reduced neovascular outgrowth into the inner limiting membrane. Neovascular tufts and nonperfused areas were also reduced.
  
  
  CONCLUSIONS
  High expression of netrin-1 was detected in the retina under ischemic conditions and played a significant role in pathological retinal angiogenesis. Therefore, netrin-1 represents a potential therapeutic target for diabetic retinopathy, retinopathy of prematurity and other ocular neovascular diseases.
authors: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
authors: Huizhuo
authors: H
authors: Xu
authors: Jiaolian
authors: J
authors: Liu
authors: Siqi
authors: S
authors: Xiong
authors: Yun-Zheng
authors: YZ
authors: Le
authors: Xiaobo
authors: X
authors: Xia
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000378:metabolism*; D000075388:Netrin-1; D034741:RNA, Small Interfering / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015861:Retinal Neovascularization / Q000378:metabolism / Q000628:therapy*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1