@article{b4332543571c4e9aa4e8dbd39265253f,
title = "Tie2 activation promotes choriocapillary regeneration for alleviating neovascular age-related macular degeneration",
abstract = "Choriocapillary 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.",
author = "Jaeryung Kim and Park, {Jang Ryul} and Jeongwoon Choi and Intae Park and Yoonha Hwang and Hosung Bae and Yongjoo Kim and Choi, {Woo Jhon} and Yang, {Jee Myung} and Sangyeul Han and Chung, {Tae Young} and Pilhan Kim and Yoshiaki Kubota and Augustin, {Hellmut G.} and Oh, {Wang Yuhl} and Koh, {Gou Young}",
note = "Funding Information: We thank Y. Nakaoka (Osaka University) for providing Angpt1flox/flox mice and J. Kim (Seoul National University) for assistance with statistical analysis. We dedicate this paper to G.-J. Song (The Founder of Kyung-Ahm Education and Culture Foundation) who is suffering from NV-AMD on his heartfelt encouragement for this study. Funding: This study was supported by grants from the Institute for Basic Science (IBS-R025-D1-2015 to G.Y.K) funded by the Ministry of Science and ICT, Republic of Korea, from the National Research Foundation of Korea (2016M3C7A1913844 to W.-Y.O), and from the Ministry of Health and Welfare of Republic of Korea (HI15C0001 to W.-Y.O.). Publisher Copyright: Copyright {\textcopyright} 2019 The Authors.",
year = "2019",
month = feb,
day = "13",
doi = "10.1126/sciadv.aau6732",
language = "English",
volume = "5",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "2",
}