Kim, Jaeryung;
Park, Jang Ryul;
Choi, Jeongwoon;
Park, Intae;
Hwang, Yoonha;
Bae, Hosung;
Kim, Yongjoo;
... Koh, Gou Young; + view all
(2019)
Tie2 activation promotes choriocapillary
regeneration for alleviating neovascular age-related
macular degeneration.
Science Advances
, 5
(2)
, Article eaau6732. 10.1126/sciadv.aau6732.
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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.
| Type: | Article |
|---|---|
| Title: | Tie2 activation promotes choriocapillary regeneration for alleviating neovascular age-related macular degeneration |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1126/sciadv.aau6732 |
| Publisher version: | https://doi.org/10.1126/sciadv.aau6732 |
| Language: | English |
| Additional information: | Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S.Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Electronic and Electrical Eng |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10210939 |
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