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

Science Advances
Jaeryung KimGou Young Koh

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.

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Citations

Feb 6, 2020·Journal of Biophotonics·Bjorn PaulsonJun Ki Kim
Nov 3, 2020·Retina·Jeffrey S HeierCarlos Quezada-Ruiz
Apr 10, 2020·The British Journal of Ophthalmology·Thales Antonio Cabral de GuimaraesMichel Michaelides
Dec 7, 2019·ACS Chemical Biology·Peter David KochRalph Weissleder
Oct 27, 2021·EMBO Reports·Yan Ting ZhaoHannele Ruohola-Baker
Jan 17, 2020·Ophthalmic Research·Qiu-Yang ZhangBiao Yan

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Methods Mentioned

BETA
laser capture microdissection
transgenic
enzyme-linked immunosorbent assay
electrophoresis
biosensor
chip
immunoprecipitation
PCR

Software Mentioned

OCTA
R
BIAevaluation
ABTAA
R Foundation for Statistical Computing
MATLAB
GSEA
Genowiz
BIOCONDUCTOR
Bowtie2

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