CCR3 is a target for age-related macular degeneration diagnosis and therapy.
CCR3 is a target for age-related macular degeneration diagnosis and therapy.
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DOI：
10.1038/nature08151
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发表时间：
2009-07-09
期刊：
影响因子：
64.8
通讯作者：
Ambati, Jayakrishna
中科院分区：
文献类型：
--
作者：
Takeda, Atsunobu;Baffi, Judit Z.;Kleinman, Mark E.;Cho, Won Gil;Nozaki, Miho;Yamada, Kiyoshi;Kaneko, Hiroki;Albuquerque, Romulo J. C.;Dridi, Sami;Saito, Kuniharu;Raisler, Brian J.;Budd, Steven J.;Geisen, Pete;Munitz, Ariel;Ambati, Balamurali K.;Green, Martha G.;Ishibashi, Tatsuro;Wright, John D.;Humbles, Alison A.;Gerard, Craig J.;Ogura, Yuichiro;Pan, Yuzhen;Smith, Justine R.;Grisanti, Salvatore;Hartnett, M. Elizabeth;Rothenberg, Marc E.;Ambati, Jayakrishna
视网膜相关性黄斑变性（AMD）是全世界失明的主要原因，在工业化国家与癌症一样普遍。AMD中的大多数失明是由脉络膜新生血管（CNV）侵入视网膜引起的。我们报道嗜酸性粒细胞/肥大细胞趋化因子受体CCR 3在AMD患者的CNV内皮细胞中特异性表达，并且尽管其配体eotaxin-1、-2和-3表达，但人CNV中既不存在嗜酸性粒细胞也不存在肥大细胞。CCR 3或嗜酸细胞活化趋化因子的遗传或药理学靶向作用可抑制小鼠损伤诱导的CNV。通过CCR 3阻断抑制CNV是由于直接抑制内皮细胞增殖，并且与炎症解偶联，因为它发生在缺乏嗜酸性粒细胞或肥大细胞的小鼠中，并且不依赖于巨噬细胞和中性粒细胞募集。CCR 3阻断在减少CNV方面比目前临床使用的血管内皮生长因子-A（VEGF-A）中和更有效，并且与VEGF-A阻断不同，对小鼠视网膜没有毒性。体内成像与CCR 3靶向量子点定位自发CNV不可见的标准荧光素血管造影术在视网膜入侵前的小鼠。CCR 3靶向可能通过早期检测和治疗性血管抑制来减少由于AMD引起的视力丧失。
Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularization (CNV). We report that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in CNV endothelial cells in humans with AMD, and that, despite the expression of its ligands eotaxin-1, -2, and -3, neither eosinophils nor mast cells are present in human CNV. Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation as it occurred in mice lacking eosinophils or mast cells and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor-A (VEGF-A) neutralization, which is currently in clinical use, and, unlike VEGF-A blockade, not toxic to the mouse retina. In vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion. CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.
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DOI：
10.1016/j.biocel.2004.09.001
发表时间：
2005-03-01
影响因子：
4
作者：
Puxeddu, A;Alian, A;Levi-Schaffer, F
通讯作者：
Levi-Schaffer, F
影响因子：
158.5
作者：
Brown, David M.;Kaiser, Peter K.;Schneider, Susan
通讯作者：
Schneider, Susan
DOI：
10.1073/pnas.0308544100
发表时间：
2004-02-17
影响因子：
11.1
作者：
Fulkerson, PC;Zimmermann, N;Rothenberg, ME
通讯作者：
Rothenberg, ME
影响因子：
15.9
作者：
Nozaki, M;Sakurai, E;Ambati, J
通讯作者：
Ambati, J
影响因子：
158.5
作者：
Gragoudas, ES;Adamis, AP;Guyer, DR
通讯作者：
Guyer, DR