The critical role of ocular-infiltrating macrophages in the development of choroidal neovascularization.
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.
Tsutsumi
Chikako
C
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Sonoda
Koh-Hei
KH
Egashira
Kensuke
K
Qiao
Hong
H
Hisatomi
Toshio
T
Nakao
Shintaro
S
Ishibashi
Minako
M
Charo
Israel F
IF
Sakamoto
Taiji
T
Murata
Toshinori
T
Ishibashi
Tatsuro
T
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D020256:Choroidal Neovascularization; D005123:Eye / Q000098:blood supply* / Q000473:pathology; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine
C515334:CCR2 protein, human; C515335:Ccr2 protein, mouse; D006133:Growth Substances; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine