Abstract
Background: Schlemm's canal (SC) is a large vessel residing in the iridocorneal angle and is required to regulate aqueous humor outflow. Normal SC structure and function is indispensable for maintaining normal intraocular pressure, and elevated intraocular pressure is a risk factor for development of glaucoma. Recent reports have identified a key role of the angiopoietin-Tie2 pathway for SC development and function; however, the role of the orphan receptor Tie1 has not been clarified. Methods: We used Tie1 knock out mice to study the function of Tie1 in SC development and function. Real-time quantitative polymerase chain reaction and Western blot analyses were used to verify Tie1 deletion. High-resolution microscopy of mouse SC whole mount and cross sections were used to study SC morphology. Measurement of intraocular pressure in live mice was used to study the impact of Tie1 on SC function. Results: Tie1 is highly expressed in both human and mouse SC. Tie1 knock out mice display hypomorphic SC and elevated intraocular pressure as a result of attenuated SC development. Conclusions: Tie1 is indispensable for SC development and function, supporting it as a novel target for future SC-targeted glaucoma therapies and a candidate gene for glaucoma in humans.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 348-351 |
| Number of pages | 4 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Volume | 42 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2022 |
Funding
This work was supported by National Institutes of Health (NIH) RO1EY025799-05 and NIHP30DK114857 to S.E. Quaggin, NIH RO1 EY032609, a Brightfocus foundation new investigator fellowship, the Bayer Global Ophthalmology Awards Program Fellowship to B.R. Thomson, the Northwestern University Transgenic and Targeted Mutagenesis Laboratory, the Center for Advanced Microscopy of the Feinberg School of Medicine and a Cancer Center Support Grant (NCI CCSG P30 CA060553). S.E. Quaggin holds patents related to therapeutic targeting of the ANGPT-TEK pathway in ocular hypertension and glaucoma and receives research support, owns stock in and is a director of Mannin Research. S.E. Quaggin also receives consulting fees from AstraZeneca, Janssen, the Lowy Medical Research Foundation, and Roche/Genentech; is Chair of the External Scientific Advisory Board for AstraZeneca; and is a scientific advisor or member of AstraZeneca, Genentech/Roche, the Karolinska CVRM Institute, the Lowy Medical Research Institute, Mannin, Novartis, and Pfizer. B.R. Thomson has applied for a patent related to therapeutic targeting of the ANGPT-TEK pathway. Unrelated to this research, B.R. Thomson receives research funding from Bayer. The other authors report no conflicts.
Keywords
- Schlemm's canal
- Tie1
- angiopoietin
- glaucoma
- intraocular pressure
- microscopy
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine