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Endothelial Tyrosine Kinase Tie1 Is Required for Normal Schlemm's Canal Development-Brief Report
Jing Du1, Benjamin R Thomson1, Tuncer Onay1
1Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago. Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago.
The orphan receptor Tie1 is crucial for Schlemm's canal development and function. Tie1 deficiency in mice leads to abnormal Schlemm's canal structure and elevated intraocular pressure, suggesting its role in glaucoma.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Schlemm's canal (SC) regulates aqueous humor outflow, essential for maintaining intraocular pressure (IOP).
- Elevated IOP is a significant risk factor for glaucoma development.
- The angiopoietin-Tie2 pathway is implicated in SC function, but the role of the orphan receptor Tie1 remains unclear.
Purpose of the Study:
- To investigate the function of Tie1 in Schlemm's canal development and function.
- To determine the impact of Tie1 deficiency on SC morphology and IOP.
Main Methods:
- Utilized Tie1 knockout mice to study SC development and function.
- Employed real-time quantitative PCR and Western blot to confirm Tie1 deletion.
- Assessed SC morphology using high-resolution microscopy and measured IOP in live mice.
Main Results:
- Tie1 exhibits high expression in both human and mouse SC.
- Tie1 knockout mice displayed hypomorphic SC development.
- Reduced SC development in Tie1 knockout mice resulted in elevated intraocular pressure.
Conclusions:
- Tie1 is indispensable for SC development and function.
- Tie1 represents a potential therapeutic target for SC-targeted glaucoma treatments.
- Tie1 is identified as a candidate gene for human glaucoma.
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