May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Vascular Adhesion Protein-1 Blockade Suppresses Choroidal Neovascularization
Author Affiliations & Notes
  • K. Noda
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • H. She
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • T. Nakazawa
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • T. Hisatomi
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • S. Nakao
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • L. Almulki
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • J. W. Miller
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • E. S. Gragoudas
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • Y. Mashima
    R-Tech Ueno, Ltd., Tokyo, Japan
  • A. Hafezi-Moghadam
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  K. Noda, None; H. She, None; T. Nakazawa, None; T. Hisatomi, None; S. Nakao, None; L. Almulki, None; J.W. Miller, None; E.S. Gragoudas, None; Y. Mashima, R-Tech Ueno, Ltd., E; A. Hafezi-Moghadam, R-Tech Ueno, Ltd., F.
  • Footnotes
    Support  R-Tech Ueno Ltd Grant, NEI core grant EY14104, NIH grant AI050775 to A.H.M., Massachusetts Lions Foundation, and Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 539. doi:https://doi.org/
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      K. Noda, H. She, T. Nakazawa, T. Hisatomi, S. Nakao, L. Almulki, J. W. Miller, E. S. Gragoudas, Y. Mashima, A. Hafezi-Moghadam; Vascular Adhesion Protein-1 Blockade Suppresses Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2008;49(13):539. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Vascular adhesion protein-1 (VAP-1), a 170-kDa homodimeric sialylated glycoprotein, is an endothelial adhesion molecule, involved in leukocyte recruitment. Macrophages play an important role in the development of choroidal neovascularization (CNV), an integral component of age-related macular degeneration (AMD). Recently, we showed the role of VAP-1 in ocular inflammation. Here, we investigate the expression of VAP-1 in the choroid and its role in CNV development.

Methods: : Rats (8-12 weeks old) were treated in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Immunohistochemistry and RT-PCR were performed to determine whether VAP-1 was expressed in the normal choroid. CNV was induced by laser photocoagulation (150mW, 100µm, 100msec). Animals received daily injections of the VAP-1 inhibitor, U-V002 (0.3mg/kg), or vehicle control. Seven days after laser injury, choroidal flat mounts were prepared and the size of the CNV lesions was quantified. Macrophage infiltration and the levels of inflammatory cytokines were assessed 3 days after laser injury.

Results: : In normal animals, VAP-1 expression in the choroid was exclusive to the vasculature. In laser-injured animals VAP-1 also co-localized with the new vessels of the CNV lesions. Seven days after laser injury, the animals treated with the VAP-1 inhibitor showed a significant decrease in CNV size (14,536±2,175µm2), compared with vehicle-treated controls (25,026±1,586µm2, p<0.01). The number of accumulated macrophages 3 days after laser injury was significantly reduced by 41% with blockade of VAP-1 compared to vehicle-treated controls (p<0.05). VAP-1 blockade significantly reduced the expression of inflammation-associated molecules such as tumor necrosis factor (TNF)-α (p<0.05), monocyte chemoattractant protein (MCP)-1 (p<0.01) and intercellular adhesion molecule (ICAM)-1 (p<0.01).

Conclusions: : The current data indicate a role for VAP-1 in the recruitment of macrophages to CNV lesions. VAP-1 inhibition may become a novel therapeutic strategy in the treatment of ocular inflammatory diseases, such as AMD.

Keywords: choroid: neovascularization • cell adhesions/cell junctions • age-related macular degeneration 
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