マルコ　ルカ   MARUKO Ruka   丸子　留佳    所属   医学部 医学科（東京女子医科大学病院）    職種   寄附部門助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Suppression of choroidal neovascularization and quantitative and qualitative inhibition of VEGF and CCL2 by heparin.
掲載誌名	正式名：Investigative ophthalmology & visual science 略　 称：Invest Ophthalmol Vis Sci ISSNコード：15525783/01460404
掲載区分	国外
巻・号・頁	52(6),pp.3193-9
著者・共著者	Tomida Daisuke, Nishiguchi Koji M, Kataoka Keiko, Yasuma Tetsuhiro R, Iwata Eiji, Uetani Ruka, Kachi Shu, Terasaki Hiroko
発行年月	2011/05
概要	PURPOSE:To study the effect of heparin on the development of laser-induced choroidal neovascularization (CNV) and to assess the underlying molecular mechanisms.METHODS:Bone marrow transplantation (BMT) was conducted by intravenous injection of green fluorescence protein (GFP)-labeled bone marrow cells (1 × 10(7) cells) into irradiated (9 Gy) C57BL/6J mice. Laser photocoagulation was applied to induce CNV; subsequently, unfractionated heparin or phosphate-buffered saline was injected into mice that did or did not undergo BMT. The area of CNV, distribution of injected heparin, and quantities of infiltrating cells positive for Griffonia simplicifolia (GS) and GFP inside and outside the CNV were evaluated. Effects of heparin on the secretion of VEGF, CCL2, and TNF-α by ARPE19 cells and on the binding of VEGF, CCL2, TNF-α, and their receptors were analyzed in vitro.RESULTS:Intravitreal injection of heparin at higher doses reduced the size of the CNV. Heparin localized at the vascular structures and photoreceptor layers adjacent to the laser scar. Only GS-positive cells infiltrating outside the CNV were reduced significantly, but not those inside the CNV or those expressing GFP. Relative decreases in VEGF and CCL2 levels were observed in media of ARPE19 cells at higher heparin concentrations. In vitro binding assays revealed that heparin and porcine ocular fluid, respectively, suppressed the binding of VEGF to VEGFR2 and CCL2 to CCR2.CONCLUSIONS:Intravitreal heparin injection inhibited CNV development. Reduced VEGF and CCL2 secretion by RPE cells and suppression of VEGF-VEGFR2 and CCL2-CCR2 interactions at the laser site mediated by heparin may contribute to the pharmacologic effect.
DOI	10.1167/iovs.10-6737
PMID	21296829