All TIEd up: mechanisms of Schlemm’s canal maintenance
Jeremiah Bernier-Latmani, Tatiana V. Petrova
Jeremiah Bernier-Latmani, Tatiana V. Petrova
Published October 2, 2017; First published September 18, 2017
Citation Information: J Clin Invest. 2017;127(10):3594-3597. https://doi.org/10.1172/JCI96840.
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Commentary

All TIEd up: mechanisms of Schlemm’s canal maintenance

Abstract

Glaucoma is a leading cause of blindness, with an estimated world-wide prevalence of 3.5% in members of the population older than 40 years of age. Elevated intraocular pressure as the result of abnormal resistance to aqueous humor drainage is a major contributing, and the only preventable, factor in glaucoma development. Schlemm’s canal (SC), a lymphatic-like vessel encircling the anterior portion of the eye, plays a key role in promoting aqueous humor outflow and maintenance of normal intraocular pressure. The risk of developing glaucoma increases with age; therefore, understanding mechanisms of SC maintenance and how aging affects SC function are of special importance, both for prevention and novel treatment approaches to glaucoma. Using a compelling array of genetic models, Kim et al. report in this issue of the JCI that continuous angiopoietin/TIE2 signaling is required for maintaining SC identity and integrity during adulthood and show that its age-related changes can be rescued by a TIE2 agonistic antibody.

Authors

Jeremiah Bernier-Latmani, Tatiana V. Petrova

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Figure 1

Role of the ANGPT/TIE2 pathway in maintenance of SC.

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Role of the ANGPT/TIE2 pathway in maintenance of SC. Aqueous humor (AH) ...
Aqueous humor (AH) produced by ciliary body epithelium is drained primarily via TM and SC situated at the iridocorneal angle of the eye. Equilibrium between AH production and drainage is essential for maintenance of normal IOP. Under normal conditions in which Tie2 can actively signal, ECs of the inner wall of SC, juxtaposed to TM, are subjected to the gradients of pressure and AH flow. They are characterized by high expression of PROX1, TIE2, VEGFR3, and KLF4 and the presence of giant vacuoles, pressure-dependent EC outpouches that provide a passageway for AH flow across SC wall. SC mural cells and the TM are sources of ANGPT1 and -2, respectively. ANGPT/TIE2 signaling maintains SC integrity and function; its inactivation leads to loss of SC EC specialization, including decreased expression of PROX1, VEGFR3, and KLF4, and ultimately results in SC degeneration and increased IOP.