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, Woo Jhon Choi, Jee Myung Yang, Sangyeul Han, Tae Young Chung, Pilhan Kim, Yoshiaki Kubota, Hellmut G. Augustin, Wang Yuhl Oh, Gou Young Koh

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Article numbereaau6732
JournalScience Advances
Volume5
Issue number2
DOIs
Publication statusPublished - 2019 Feb 13

ASJC Scopus subject areas

  • Physics and Astronomy (miscellaneous)
  • General

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    Kim, J., Park, J. R., Choi, J., Park, I., Hwang, Y., Bae, H., Kim, Y., Choi, W. J., Yang, J. M., Han, S., Chung, T. Y., Kim, P., Kubota, Y., Augustin, H. G., Oh, W. Y., & Koh, G. Y. (2019). Tie2 activation promotes choriocapillary regeneration for alleviating neovascular age-related macular degeneration. Science Advances, 5(2), [eaau6732]. https://doi.org/10.1126/sciadv.aau6732