Journal Article

DKFZ-2020-00716

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Tie2 activation promotes choriocapillary regeneration for alleviating neovascular age-related macular degeneration.

Kim, J. ; Park, J. R. ; Choi, J. ; Park, I. ; Hwang, Y. ; Bae, H. ; Kim, Y. ; Choi, W. ; Yang, J. M. ; Han, S. ; Chung, T.-Y. ; Kim, P. ; Kubota, Y. ; Augustin, H.DKFZ* ; Oh, W.-Y. ; Koh, G. Y.

2019
Assoc. Washington, DC [u.a.]

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Please use a persistent id in citations: doi:10.1126/sciadv.aau6732

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.

Keyword(s): Angiopoietin-1 ; Angpt1 protein, mouse ; Vascular Endothelial Growth Factor A ; Receptor, TIE-2 ; Tek protein, mouse

Note: DKFZ-ZMBH Alliance

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Contributing Institute(s):

1. A190 Vaskuläre Onkologie und Metastatistierung (A190)

Research Program(s):

1. 311 - Signalling pathways, cell and tumor biology (POF3-311) (POF3-311)

Appears in the scientific report 2019

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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