# Roles of CaSR in ocular surface health and disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $396,242

## Abstract

ABSTRACT
Dry eye disease (DED) is a major health problem. Reduced ocular surface hydration is a key pathology in
DED, which causes symptoms and can lead to ocular surface inflammation and damage. Current FDA-
approved treatments for DED include artificial tears and anti-inflammatory agents that have variable and limited
efficacy. Here we propose a novel target for treatment of DED. The target is the extracellular Ca2+-sensing
receptor (CaSR) that has well-known modulatory effects on epithelial ion transport in various tissues such as
intestine and kidney. We found prominent CaSR expression in mouse and human corneal and conjunctival
epithelial cells. CaSR activation in the ocular surface reduced CFTR-mediated Cl- secretion, confirming key
roles of CaSR ocular surface ion transport. Importantly, we found that CaSR inhibition by NPS-2143 stimulates
CFTR-mediated Cl- secretion in the ocular surface and increases tear fluid volume in mice by ~100%. Here we
will perform key translational studies for CaSR inhibitors, by testing them in clinically relevant animal and
human cell models of DED to advance them towards clinical testing (Aim 1). We will also study the roles and
mechanisms of CaSR effect in ocular surface ion transport and health (Aim 2). The proposed studies can
potentially lead to clinical testing of CaSR inhibitors for DED in the very near future. By identifying a novel
treatment, these studies can ultimately reduce DED morbidity. Lastly, by identifying roles and mechanisms of
CaSR in ocular surface, this project can also identify novel disease mechanisms for DED.

## Key facts

- **NIH application ID:** 10859479
- **Project number:** 1R01EY036139-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Onur Cil
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $396,242
- **Award type:** 1
- **Project period:** 2024-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10859479

## Citation

> US National Institutes of Health, RePORTER application 10859479, Roles of CaSR in ocular surface health and disease (1R01EY036139-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10859479. Licensed CC0.

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