Vascular adhesion protein-1 blockade suppresses choroidal neovascularization.
Vascular adhesion protein-1 (VAP-1) is an endothelial cell adhesion molecule involved in leukocyte recruitment. Leukocytes and, in particular, macrophages play an important role in the development of choroidal neovascularization (CNV), an integral component of age-related macular degeneration (AMD). Previously, we showed a role for VAP-1 in ocular inflammation. Here, we investigate the expression of VAP-1 in the choroid and its role in CNV development. VAP-1 was expressed in the choroid, exclusively in the vessels, and colocalized in the vessels of the CNV lesions. VAP-1 blockade with a novel and specific inhibitor significantly decreased CNV size, fluorescent angiographic leakage, and the accumulation of macrophages in the CNV lesions. Furthermore, VAP-1 blockade significantly reduced the expression of inflammation-associated molecules such as tumor necrosis factor (TNF) -alpha, monocyte chemoattractant protein (MCP) -1, and intercellular adhesion molecule (ICAM) -1. This work provides evidence for an important role of VAP-1 in the recruitment of macrophages to CNV lesions, establishing a novel link between VAP-1 and angiogenesis. Inhibition of VAP-1 may become a new therapeutic strategy in the treatment of AMD.
Noda
Kousuke
K
Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
She
Haicheng
H
Nakazawa
Toru
T
Hisatomi
Toshio
T
Nakao
Shintaro
S
Almulki
Lama
L
Zandi
Souska
S
Miyahara
Shinsuke
S
Ito
Yasuhiro
Y
Thomas
Kennard L
KL
Garland
Rebecca C
RC
Miller
Joan W
JW
Gragoudas
Evangelos S
ES
Mashima
Yukihiko
Y
Hafezi-Moghadam
Ali
A
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement; D020256:Choroidal Neovascularization / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D008268:Macular Degeneration / Q000209:etiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015815:Cell Adhesion Molecules; D017931:DNA Primers; D018836:Inflammation Mediators; D012333:RNA, Messenger; D006631:Amine Oxidase (Copper-Containing); C510433:vascular adhesion protein-1, rat