Details

Autor(en) / Beteiligte

• Noda, Kousuke
• Miyahara, Shinsuke
• Nakazawa, Toru
• Almulki, Lama
• Nakao, Shintaro
• Hisatomi, Toshio
• She, Haicheng
• Thomas, Kennard L
• Garland, Rebecca C
• Miller, Joan W
• Gragoudas, Evangelos S
• Kawai, Yosuke
• Mashima, Yukihiko
• Hafezi-Moghadam, Ali

Titel

Inhibition of vascular adhesion protein-1 suppresses endotoxin-induced uveitis

Ist Teil von

• The FASEB journal, 2008-04, Vol.22 (4), p.1094-1103

Ort / Verlag

United States: The Federation of American Societies for Experimental Biology

Erscheinungsjahr

2008

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Inflammatory leukocyte accumulation is a common feature of major ocular diseases, such as uveitis, diabetic retinopathy, and age-related macular degeneration. Vascular adhesion protein-1 (VAP-1), a cell surface and soluble molecule that possesses semicarbazide-sensitive amine oxidase (SSAO) activity, is involved in leukocyte recruitment. However, the expression of VAP-1 in the eye and its contribution to ocular inflammation are unknown. Here, we investigated the role of VAP-1 in an established model of ocular inflammation, the endotoxin-induced uveitis (EIU), using a novel and specific inhibitor. Our inhibitor has a half-maximal inhibitory concentration (IC₅₀) of 0.007 μM against human and 0.008 μM against rat SSAO, while its IC₅₀ against the functionally related monoamine oxidase (MAO) -A and MAO-B is >10 μM. In the retina, VAP-1 was exclusively expressed in the vasculature, and its expression level was elevated during EIU. VAP-1 inhibition in EIU animals significantly suppressed leukocyte recruitment to the anterior chamber, vitreous, and retina, as well as retinal endothelial P-selectin expression. Our data suggest an important role for VAP-1 in the recruitment of leukocytes to the immune-privileged ocular tissues during acute inflammation. VAP-1 inhibition may become a novel strategy in the treatment of ocular inflammatory diseases.--Noda, K., Miyahara, S., Nakazawa, T., Almulki, L., Nakao, S., Hisatomi, T., She, H., Thomas, K. L., Garland, R. C., Miller, J. W., Gragoudas, E. S., Kawai, Y., Mashima, Y., Hafezi-Moghadam, A. Inhibition of vascular adhesion protein-1 suppresses endotoxin-induced uveitis.