Related Experiment Video
Updated: Jul 10, 2025
13:47
Laser Capture Microdissection of Highly Pure Trabecular Meshwork from Mouse Eyes for Gene Expression Analysis
Published on: June 3, 2018
9.4K
TIE1 and TEK signalling, intraocular pressure, and primary open-angle glaucoma: a Mendelian randomization study
Skanda Rajasundaram1,2, Nazlee Zebardast3,4, Puja Mehta5,6,7
1Faculty of Medicine, Imperial College London, London, UK. skandarajasundaram@gmail.com.
Journal of Translational Medicine
|November 24, 2023
Summary
This study found that TIE1 and TEK signaling in humans causally influence intraocular pressure (IOP). Increased TIE1 signaling lowers IOP, suggesting TIE1 as a potential therapeutic target for glaucoma.
Area of Science:
- Ophthalmology
- Genetics
- Vascular Biology
Background:
- Primary open-angle glaucoma (POAG) management relies on lowering intraocular pressure (IOP).
- Schlemm's canal (SC) regulates aqueous humor drainage, with animal studies implicating angiopoietin-TEK and TIE1 signaling in IOP control.
- Human genetic evidence for TIE1 and TEK's role in IOP regulation was previously lacking.
Purpose of the Study:
- To investigate the human genetic basis for TIE1 and TEK signaling in regulating IOP and POAG.
- To determine if genetic variations in TIE1 and TEK influence IOP and POAG risk.
- To explore the therapeutic potential of targeting TIE1/TEK pathways for IOP reduction.
Main Methods:
- Utilized Mendelian randomization (MR) with GWAS data for soluble TIE1 (sTIE1), soluble TEK (sTEK), IOP, and POAG.
- Performed genetic colocalization to assess shared or distinct causal variants for TIE1/TEK signaling and IOP/POAG.
- Analyzed single-nucleus RNA-sequencing data to examine TIE1 and TEK expression in the human ocular anterior segment.
Main Results:
- Elevated genetically proxied TIE1 signaling correlated with reduced IOP (-0.21 mmHg per SD increase in sTIE1).
- Decreased genetically proxied TEK signaling also correlated with reduced IOP (-0.14 mmHg per SD decrease in sTEK).
- Colocalization analysis indicated a higher probability of a shared causal variant for TIE1 and IOP (PP_shared=0.98) compared to TEK and IOP (PP_shared=0.30).
- TIE1 and TEK were found to be preferentially expressed in the endothelium of Schlemm's canal, lymphatic, and vascular structures in the anterior segment.
Conclusions:
- This study provides novel human genetic evidence supporting a causal role for TIE1 and TEK signaling in IOP regulation.
- Combined MR and colocalization analyses suggest TIE1 signaling has a stronger association with IOP than TEK signaling.
- TIE1 emerges as a more promising therapeutic target for lowering IOP compared to TEK.
Related Concept Videos
01:27Open Angle Glaucoma: Treatment
458
In open-angle glaucoma, the iridocorneal angle remains open, but the trabecular meshwork becomes stiff, slowing down the outflow of aqueous humor. This causes a buildup of aqueous humor in the anterior chamber, leading to a sudden increase in intraocular pressure. The treatment for open-angle glaucoma focuses on reducing the elevated intraocular pressure by either decreasing the secretion of aqueous humor or increasing its outflow.
Drugs such as carbonic anhydrase inhibitors, α2- and...
Drugs such as carbonic anhydrase inhibitors, α2- and...
458
01:25Glaucoma: Overview
594
Glaucoma is an eye condition characterized by increased intraocular pressure that damages the retina and optic nerve, leading to irreversible blindness if left untreated. The human eye has various components, including the cornea, iris, pupil, lens, and optic nerve. Aqueous humor is secreted by the epithelium of the ciliary body in the posterior chamber and flows through the trabecular meshwork and canal of Schlemm, maintaining normal intraocular pressure. The trabecular meshwork and the canal...
594
01:28Angle Closure Glaucoma: Treatment
528
Angle-closure glaucoma, or closed-angle glaucoma, is an eye condition where the iris bulges out and blocks the iridocorneal angle, resulting in a buildup of aqueous humor and increased intraocular pressure. Immediate medical attention is necessary due to the sudden onset of symptoms. The treatment for angle-closure glaucoma includes short-term and long-term approaches. Short-term treatment involves using eye drops like pilocarpine to lower intraocular pressure by increasing aqueous humor...
528