Impaired angiopoietin/Tie2 signaling compromises Schlemm's canal integrity and induces glaucoma

Jaeryung Kim, Dae Young Park, Hosung Bae, Do Young Park, Dongkyu Kim, Choong Kun Lee, Sukhyun Song, Tae Young Chung, Dong Hui Lim, Yoshiaki Kubota, Young Kwon Hong, Yulong He, Hellmut G. Augustin, Guillermo Oliver, Gou Young Koh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Primary open-angle glaucoma (POAG) is often caused by elevated intraocular pressure (IOP), which arises due to increased resistance to aqueous humor outflow (AHO). Aqueous humor flows through Schlemm's canal (SC), a lymphatic-like vessel encircling the cornea, and via intercellular spaces of ciliary muscle cells. However, the mechanisms underlying increased AHO resistance are poorly understood. Here, we demonstrate that signaling between angiopoietin (Angpt) and the Angpt receptor Tie2, which is critical for SC formation, is also indispensable for maintaining SC integrity during adulthood. Deletion of Angpt1/Angpt2 or Tie2 in adult mice severely impaired SC integrity and transcytosis, leading to elevated IOP, retinal neuron damage, and impairment of retinal ganglion cell function, all hallmarks of POAG in humans. We found that SC integrity is maintained by interconnected and coordinated functions of Angpt-Tie2 signaling, AHO, and Prox1 activity. These functions diminish in the SC during aging, leading to impaired integrity and transcytosis. Intriguingly, Tie2 reactivation using a Tie2 agonistic antibody rescued the POAG phenotype in Angpt1/Angpt2-deficient mice and rejuvenated the SC in aged mice. These results indicate that the Angpt-Tie2 system is essential for SC integrity. The impairment of this system underlies POAGassociated pathogenesis, supporting the possibility that Tie2 agonists could be a therapeutic option for glaucoma.

Original languageEnglish (US)
Pages (from-to)3877-3896
Number of pages20
JournalJournal of Clinical Investigation
Issue number10
StatePublished - Oct 2 2017

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Impaired angiopoietin/Tie2 signaling compromises Schlemm's canal integrity and induces glaucoma'. Together they form a unique fingerprint.

Cite this