PMID- 21813636
OWN - NLM
STAT- MEDLINE
DCOM- 20111109
LR  - 20181228
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 52
IP  - 10
DP  - 2011 Sep 14
TI  - The antiangiogenic effects of integrin alpha5beta1 inhibitor (ATN-161) in vitro 
      and in vivo.
PG  - 7213-20
LID - 10.1167/iovs.10-7097 [doi]
AB  - PURPOSE: Integrin alpha5beta1 is involved in the development of choroidal 
      neovascularization (CNV). Thus, the inhibition of integrin alpha5beta1 may provide an 
      alternative to the current standard of CNV therapy, which involves inhibition of 
      vascular endothelial growth factor (VEGF) and is not effective in all patients. 
      This study evaluated the antiangiogenic effects of ATN-161, a small peptide 
      inhibitor of integrin alpha5beta1, in human choroidal endothelial cells (hCECs) and in 
      laser-induced CNV in rats. Furthermore, the utility of spectral-domain optical 
      coherence tomography (SD-OCT) for dynamic observation of the development of CNV 
      in animal models was assessed. METHODS: The antiangiogenic potential of ATN-161 
      was evaluated in VEFG-stimulated hCECs by MTS proliferation assays, migration 
      assays, and synthetic matrix capillary tube formation assays. To evaluate the 
      antiangiogenic effects of ATN-161 in vivo, CNV was induced in rats by laser 
      photocoagulation. ATN-161, scrambled peptide, or AF564 anti-VEGF antibody, were 
      injected intravitreally immediately after photocoagulation. Eyes were examined by 
      SD-OCT and fluorescein angiography on days 1, 7, and 14 after injection, and the 
      areas of CNV were measured by analysis of choroidal flatmounts at day 14. 
      RESULTS: ATN-161 inhibited VEGF-induced migration and capillary tube formation in 
      hCECs, but did not inhibit proliferation. In vivo, injection of ATN-161 after 
      laser photocoagulation inhibited CNV leakage and neovascularization to an extent 
      similar to AF564. Furthermore, SD-OCT and histologic examinations indicated that 
      ATN-161 significantly decreased the size of laser-induced lesions. CONCLUSIONS: 
      Integrin alpha5beta1 inhibition by ATN-161 may be a promising alternative therapy for 
      CNV-related angiogenesis. In addition, SD-OCT technology allows excellent 
      visualization of experimentally induced CNV in vivo.
FAU - Wang, Wenqiu
AU  - Wang W
AD  - Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiaotong 
      University, Shanghai, China.
FAU - Wang, Fenghua
AU  - Wang F
FAU - Lu, Fengqing
AU  - Lu F
FAU - Xu, Shan
AU  - Xu S
FAU - Hu, Weiting
AU  - Hu W
FAU - Huang, Jiannan
AU  - Huang J
FAU - Gu, Qing
AU  - Gu Q
FAU - Sun, Xiaodong
AU  - Sun X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110914
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Integrin alpha5beta1)
RN  - 0 (Oligopeptides)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, rat)
RN  - XW0H5LE42K (acetyl-prolyl-histidyl-seryl-cysteinyl-asparaginamide)
SB  - IM
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Animals
MH  - Blotting, Western
MH  - Capillaries/drug effects/physiology
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Choroid/blood supply
MH  - Choroidal Neovascularization/*drug therapy/metabolism
MH  - Disease Models, Animal
MH  - Endothelium, Vascular/*drug effects/pathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fluorescein Angiography
MH  - Humans
MH  - Integrin alpha5beta1/*antagonists & inhibitors
MH  - Laser Coagulation
MH  - Oligopeptides/*pharmacology
MH  - Rats
MH  - Rats, Inbred BN
MH  - Tomography, Optical Coherence
MH  - Vascular Endothelial Growth Factor A/metabolism/toxicity
EDAT- 2011/08/05 06:00
MHDA- 2011/11/10 06:00
CRDT- 2011/08/05 06:00
PHST- 2011/08/05 06:00 [entrez]
PHST- 2011/08/05 06:00 [pubmed]
PHST- 2011/11/10 06:00 [medline]
AID - iovs.10-7097 [pii]
AID - 10.1167/iovs.10-7097 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2011 Sep 14;52(10):7213-20. doi: 10.1167/iovs.10-7097.