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000154376 0247_ $$2doi$$a10.1126/sciadv.aau6732
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000154376 1001_ $$00000-0002-8003-5849$$aKim, Jaeryung$$b0
000154376 245__ $$aTie2 activation promotes choriocapillary regeneration for alleviating neovascular age-related macular degeneration.
000154376 260__ $$aWashington, DC [u.a.]$$bAssoc.$$c2019
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000154376 520__ $$aChoriocapillary loss is a major cause of neovascular age-related macular degeneration (NV-AMD). Although vascular endothelial growth factor (VEGF) blockade for NV-AMD has shown beneficial outcomes, unmet medical needs for patients refractory or tachyphylactic to anti-VEGF therapy exist. In addition, the treatment could exacerbate choriocapillary rarefaction, necessitating advanced treatment for fundamental recovery from NV-AMD. In this study, Tie2 activation by angiopoietin-2-binding and Tie2-activating antibody (ABTAA) presents a therapeutic strategy for NV-AMD. Conditional Tie2 deletion impeded choriocapillary maintenance, rendering eyes susceptible to NV-AMD development. Moreover, in a NV-AMD mouse model, ABTAA not only suppressed choroidal neovascularization (CNV) and vascular leakage but also regenerated the choriocapillaris and relieved hypoxia. Conversely, VEGF blockade degenerated the choriocapillaris and exacerbated hypoxia, although it suppressed CNV and vascular leakage. Together, we establish that angiopoietin-Tie2 signaling is critical for choriocapillary maintenance and that ABTAA represents an alternative, combinative therapeutic strategy for NV-AMD by alleviating anti-VEGF adverse effects.
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000154376 650_7 $$2NLM Chemicals$$aAngiopoietin-1
000154376 650_7 $$2NLM Chemicals$$aAngpt1 protein, mouse
000154376 650_7 $$2NLM Chemicals$$aVascular Endothelial Growth Factor A
000154376 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aReceptor, TIE-2
000154376 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aTek protein, mouse
000154376 7001_ $$00000-0002-5044-3278$$aPark, Jang Ryul$$b1
000154376 7001_ $$aChoi, Jeongwoon$$b2
000154376 7001_ $$aPark, Intae$$b3
000154376 7001_ $$aHwang, Yoonha$$b4
000154376 7001_ $$00000-0001-5848-7972$$aBae, Hosung$$b5
000154376 7001_ $$00000-0001-9114-9086$$aKim, Yongjoo$$b6
000154376 7001_ $$aChoi, WooJhon$$b7
000154376 7001_ $$00000-0001-5729-2233$$aYang, Jee Myung$$b8
000154376 7001_ $$00000-0002-2762-6340$$aHan, Sangyeul$$b9
000154376 7001_ $$aChung, Tae-Young$$b10
000154376 7001_ $$00000-0001-8388-1840$$aKim, Pilhan$$b11
000154376 7001_ $$00000-0001-6672-4122$$aKubota, Yoshiaki$$b12
000154376 7001_ $$0P:(DE-He78)2e92d0ae281932fc7347d819fec36b0b$$aAugustin, Hellmut$$b13$$udkfz
000154376 7001_ $$aOh, Wang-Yuhl$$b14
000154376 7001_ $$00000-0002-1231-1485$$aKoh, Gou Young$$b15
000154376 773__ $$0PERI:(DE-600)2810933-8$$a10.1126/sciadv.aau6732$$gVol. 5, no. 2, p. eaau6732 -$$n2$$peaau6732 -$$tScience advances$$v5$$x2375-2548$$y2019
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