# Does VECAD at Schlemm canal cell-junctions determine IOP and glaucoma risk?

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $698,220

## Abstract

High IOP is a major causal risk factor for glaucoma and is the target of all current glaucoma
therapies. This project investigates pathways that control intraocular pressure. Abnormalities in
these pathways contribute to glaucoma. By characterizing pathways that control IOP using
mutant mice, we expect to better understand glaucoma risk at a molecular level and will provide
important new models for studying IOP and glaucoma. Characterization of important regulatory
models will improve understanding and ultimately guide new treatments. New and more
effective IOP-lowering treatments are needed. In glaucoma, elevated IOP results from
increased resistance to aqueous humor (AQH) drainage at the inner wall of Schlemm’s canal
(SC). The inner- wall endothelial cells of SC (SECs) are the final barrier to AQH exit into the
ocular vasculature and are critical in controlling AQH outflow. Approved medications do not
directly target the inner wall or the fundamental pathology that increases outflow resistance in
glaucoma. To correct this, greater knowledge of SC biology is required and we will assess the
role of mechanotransduction in determining IOP. Abnormal mechanotransduction may result in
elevated IOP and glaucoma. A central player in endothelial mechanotransduction is the
adherens junction complex (AJC) of which VECADHERIN (VECAD) is a critical protein.
Although SECs express VECAD and AJC proteins, the role of these proteins in determining
AQH outflow is not yet demonstrated. We will test the hypothesis that the VECAD is required for
AJC mechanotransduction in SECs, controlling AQH outflow and IOP. Our preliminary data
support this hypothesis. We will test our hypothesis in the following aims: Aim 1) Determine if
AJC protein phosphorylation/ signaling adaptively responds to IOP changes in vivo. Aim 2):
Determine the role of VECAD in regulating IOP in vivo. Studying mice with mutant version of
VECAD will provide key information about its functions and may provide valuable new models of
glaucoma. Aim 3) Determine the role of phosphorylation of specific tyrosine residues in VECAD
in IOP regulation. We will assess the roles of key tyrosines in vivo by using mutant mice where
individual tyrosine residues have been mutated to phenylalanine.

## Key facts

- **NIH application ID:** 10319958
- **Project number:** 5R01EY032062-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** SIMON W JOHN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $698,220
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10319958

## Citation

> US National Institutes of Health, RePORTER application 10319958, Does VECAD at Schlemm canal cell-junctions determine IOP and glaucoma risk? (5R01EY032062-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10319958. Licensed CC0.

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