# The role of primary cilia in glaucoma pathogenesis

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $295,813

## Abstract

   
DESCRIPTION (provided by applicant): Glaucoma is a leading cause of irreversible blindness in the world. Elevated intraocular pressure (IOP) is a strong risk factor and remains the only modifiable target for intervention. However, the mechanisms causing elevated IOP remain poorly understood. Using Oculocerebrorenal syndrome of Lowe, a rare X-linked disease that presents with congenital glaucoma, we have found evidence that OCRL is an important regulator of trafficking in the eye that controls IOP. OCRL is an inositol phosphatase mutated in Lowe syndrome. OCRL localizes within the primary cilium, a subcellular organelle that plays a mechanosensory role in fluid flow. We have identified patients with Lowe syndrome who are born with congenital glaucoma and have characterized their mutations. We discovered that OCRL interacts with TRPV4, a mechanosensory channel in the primary cilia and that modulation of TRPV4 affects IOP in mice. Thus we hypothesize that OCRL plays a critical role in the recruitment of TRPV4 to the cilia in the trabecular meshwork to regulate aqueous outflow. Our aims are to (1) determine the mechanism of OCRL transport in the primary cilium in the trabecular meshwork, (2) determine the functional role of OCRL and TRPV4 interaction in the primary cilium, (3) determine whether targeting TRPV4 can reduce IOP in murine models. The experiments of this proposal may facilitate the discovery of new glaucoma therapies that can reduce the burden of blindness.

## Key facts

- **NIH application ID:** 9955272
- **Project number:** 5R01EY025295-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Yang Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $295,813
- **Award type:** 5
- **Project period:** 2017-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955272

## Citation

> US National Institutes of Health, RePORTER application 9955272, The role of primary cilia in glaucoma pathogenesis (5R01EY025295-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9955272. Licensed CC0.

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