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

Jaeryung Kim; Jang Ryul Park; Jeongwoon Choi; Intae Park; Yoonha Hwang; Hosung Bae; Yongjoo Kim; WooJhon Choi; Jee Myung Yang; Sangyeul Han; Tae-Young Chung; Pilhan Kim; Yoshiaki Kubota; Hellmut G Augustin; Wang-Yuhl Oh; Gou Young Koh

doi:10.1126/sciadv.aau6732

Back

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

Journal article

Peer reviewed

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

Jaeryung Kim, Jang Ryul Park, Jeongwoon Choi, Intae Park, Yoonha Hwang, Hosung Bae, Yongjoo Kim, WooJhon Choi, Jee Myung Yang, Sangyeul Han, …

Science advances, Vol.5(2), p.eaau6732

02/01/2019

DOI: 10.1126/sciadv.aau6732

PMID: 30788433

Files and links (1)

url

https://doi.org/10.1126/sciadv.aau6732View

Published (Version of record) Open Access

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 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.

Age Factors

Angiopoietin-1 - genetics

Angiopoietin-1 - metabolism

Animals

Animals, Genetically Modified

Choroidal Neovascularization - etiology

Choroidal Neovascularization - pathology

Disease Models, Animal

Disease Susceptibility

Fluorescent Antibody Technique

Gene Deletion

Gene Expression Profiling

Gene Expression Regulation - drug effects

Hypoxia - genetics

Hypoxia - metabolism

Macular Degeneration - etiology

Macular Degeneration - metabolism

Macular Degeneration - pathology

Macular Degeneration - physiopathology

Mice

Models, Biological

Protein Binding

Receptor, TIE-2 - genetics

Receptor, TIE-2 - metabolism

Regeneration

Signal Transduction

Transcriptional Activation - drug effects

Vascular Endothelial Growth Factor A - antagonists & inhibitors

Vascular Endothelial Growth Factor A - metabolism

Vision Disorders - genetics

Vision Disorders - parasitology

Details

Title: Subtitle: Tie2 activation promotes choriocapillary regeneration for alleviating neovascular age-related macular degeneration
Creators: Jaeryung Kim - Korea Advanced Institute of Science and Technology
Jang Ryul Park - Korea Advanced Institute of Science and Technology
Jeongwoon Choi - Korea Advanced Institute of Science and Technology
Intae Park - Institute for Basic Science
Yoonha Hwang - Korea Advanced Institute of Science and Technology
Hosung Bae - Korea Advanced Institute of Science and Technology
Yongjoo Kim - Korea Advanced Institute of Science and Technology
WooJhon Choi - Korea Advanced Institute of Science and Technology
Jee Myung Yang - Korea Advanced Institute of Science and Technology
Sangyeul Han - Institute for Basic Science
Tae-Young Chung - Samsung Medical Center
Pilhan Kim - Korea Advanced Institute of Science and Technology
Yoshiaki Kubota - Keio University
Hellmut G Augustin - German Cancer Research Center
Wang-Yuhl Oh - KI for Health Science and Technology (KIHST), KAIST, Daejeon 34141, Republic of Korea
Gou Young Koh - Korea Advanced Institute of Science and Technology
Resource Type: Journal article
Publication Details: Science advances, Vol.5(2), p.eaau6732
DOI: 10.1126/sciadv.aau6732
PMID: 30788433
ISSN: 2375-2548
eISSN: 2375-2548
Language: English
Date published: 02/01/2019
Academic Unit: Internal Medicine
Record Identifier: 9985217135402771

Metrics

1 Record Views

67 Times Cited - Web of Science