title: Intravitreal TSG-6 suppresses laser-induced choroidal neovascularization by inhibiting CCR2+ monocyte recruitment.
abstract: Choroidal neovascularization (CNV) is the hallmark of wet age-related macular degeneration (AMD), one of the leading causes of blindness in the elderly. Although the pathogenesis of CNV is not clear, a number of studies show that ocular-infiltrating macrophages and inflammation play a critical role in the development of CNV. TNFα-stimulated gene/protein (TSG)-6 is a multifunctional endogenous protein that has anti-inflammatory activities partly by regulating macrophage activation. Therefore, we here investigated the therapeutic potential of TSG-6 in a rat model of CNV induced by laser photocoagulation. Time course analysis showed that the expression of VEGF and pro-inflammatory cytokines in the choroid was up-regulated early after laser injury, and gradually decreased to baseline over 14 days. An intravitreal injection of TSG-6 suppressed the expression of VEGF and pro-inflammatory cytokines including CCL2, and reduced the size of CNV. Also, the number of Iba(+) and CCR2(+) cells including infiltrating macrophages was markedly lower in the CNV lesion of TSG-6-treated eyes. Further analysis identified CCR2(+) CD11b(+) CD11c(+) cells and CCR2(+) CD11b(-)CD11c(+) cells as the cell populations that were increased by laser injury and reduced by TSG-6 treatment. Together, the results demonstrate that TSG-6 inhibits inflammation and CCR2(+) monocyte recruitment into the choroid, and suppresses the development of CNV.
authors.affiliation: 1] Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea [2] Samsung Biomedical Research Institute, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: 1] Department of Ophthalmology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea [2] Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Samsung Biomedical Research Institute, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Yun
authors.affiliation: 1] Department of Ophthalmology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea [2] Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Ko
authors.affiliation: Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea.
authors.forename: Da Ye
authors.initials: DY
authors.lastname: Choi
authors.affiliation: 1] Department of Ophthalmology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea [2] Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Oh
mesh_terms: D000818:Animals; D016570:Bruch Membrane / Q000528:radiation effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002829:Choroid / Q000187:drug effects* / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007834:Lasers; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D054390:Receptors, CCR2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C515336:Ccr2 protein, rat; D015815:Cell Adhesion Molecules; D016207:Cytokines; D054390:Receptors, CCR2; D011994:Recombinant Proteins; C513056:Tnfaip6 protein, rat; D042461:Vascular Endothelial Growth Factor A