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혈관 연구단
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Tie2 activation promotes choriocapillary regeneration for alleviating neovascular age-related macular degeneration

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Title
Tie2 activation promotes choriocapillary regeneration for alleviating neovascular age-related macular degeneration
Author(s)
Kim J.; Park J.R.; Jeongwoon Choi; Intae Park; Hwang Y.; Hosung Bae; Kim Y.; Choi W.; Yang J.M.; Sangyeul Han; Chung T.-Y.; Kim P.; Kubota Y.; Augustin H.G.; Oh W.-Y.; Gou Young Koh
Publication Date
2019-02
Journal
SCIENCE ADVANCES, v.5, no.2, pp.eaau6732 -
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
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. Copyright © 2019 The Authors
URI
https://pr.ibs.re.kr/handle/8788114/5690
ISSN
2375-2548
Appears in Collections:
Center for Vascular Research(혈관 연구단) > Journal Papers (저널논문)
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