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Originally published online as doi:10.1189/jlb.0902436 on May 22, 2003

Published online before print May 22, 2003
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(Journal of Leukocyte Biology. 2003;74:25-32.)
© 2003 by Society for Leukocyte Biology

The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization

Chikako Tsutsumi*, Koh-Hei Sonoda*, Kensuke Egashira{dagger}, Hong Qiao*, Toshio Hisatomi*, Shintaro Nakao{ddagger}, Minako Ishibashi{dagger}, Israel F. Charo§, Taiji Sakamoto, Toshinori Murata* and Tatsuro Ishibashi*

Departments of
* Ophthalmology,
{dagger} Cardiovascular Medicine, and
{ddagger} Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
§ San Francisco General Hospital, Gladstone Institution of Cardiovascular Division, University of California; and
Department of Ophthalmology, Kagoshima University, Japan

Correspondence: Koh-Hei Sonoda, M.D., Ph.D., Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, Japan 812-8582. E-mail: sonodak{at}med.kyushu-u.ac.jp

Choroidal neovascularization (CNV) is directly related to visual loss in some eye diseases, such as age-related macular degeneration. Although several human histological studies have suggested the participation of macrophages in CNV formation, the precise mechanisms are still not fully understood. In this study, we elucidated the role of ocular-infiltrating macrophages in experimental CNV using CCR2 knockout (KO) mice, wild-type mice, and C57BL/6 (B6) mice. CCR2 is the receptor of monocyte chemoattractant protein-1, and the number of infiltrating macrophage and the area of CNV were significantly reduced in CCR2 KO mice. Enriched ocular-infiltrating macrophages from B6 mice actually showed angiogenic ability in a dorsal air sac assay. Moreover, their expression of class II, CD40, B7-1 and B7-2 molecules, and the mRNA for potential angiogenic factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor {alpha}, was also observed. Collectively, we conclude that ocular-infiltrating macrophages play an important role in CNV generation.

Key Words: photocoagulation • age-related macular degeneration • retinal pigment epithelium




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