# TRPM8 in eye health and disease

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $477,235

## Abstract

Project Summary
Dry eye disease (DED) is a complex, multifactorial disease of the ocular surface characterized by a loss of tear
film homeostasis, with symptoms including ocular discomfort and visual disturbance. DED is one of the major
reasons for visits to optometry and ophthalmology clinics in U.S., with a higher apparent incidence and
prevalence in females and the elderly. With its negative impact on quality of life, DED is a major public health
concern. Despite the gravity of DED, current treatments are limited. This strongly suggests that new targets
with novel mechanisms of action are needed. Recent studies have uncovered the role of ocular sensory
neurons in ocular physiology and the etiology of DED, especially highlighting the role of the cold and
menthol receptor, TRPM8, in ocular pain as well as basal tear flow and hydration of the ocular surface. TRPM8
is a valid target for the treatment of DED, but the complex conformational landscape of TRPM8 has hampered
drug development. Our primary objectives are to gain a comprehensive understanding of the mechanism by
which TRPM8 is gated by ligands and to design and develop novel TRPM8-modulating compounds using
structural biology, chemical biology, medicinal chemistry, in vitro and ex vivo electrophysiology, imaging, and
animal model studies. Taken together, successful completion of this work will provide the framework for
TRPM8-targeted therapeutic development as well as reveal the molecular basis for ligand gating of TRPM8 –
with far-reaching implications in treating ocular disorders.

## Key facts

- **NIH application ID:** 10801469
- **Project number:** 2R01EY031698-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Jiyong Hong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $477,235
- **Award type:** 2
- **Project period:** 2020-09-30 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801469

## Citation

> US National Institutes of Health, RePORTER application 10801469, TRPM8 in eye health and disease (2R01EY031698-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10801469. Licensed CC0.

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