# Conjunctival Goblet Cell Mucin Secretion in Inflammation and Its Resolution

> **NIH NIH R01** · SCHEPENS EYE RESEARCH INSTITUTE · 2020 · $550,751

## Abstract

Project Summary/Abstract
In response to the environment, the conjunctival goblet cells function to maintain a healthy tear film and ocular
surface, and to prevent inflammatory diseases. Goblet cells secrete the mucin MUC5AC that is protective to
the ocular surface. Goblet cells maintain an optimal mucous layer of the tear film by actively keeping it
at normal levels in health. In disease, however, mucins can be over produced as in allergic conjunctivitis. Our
laboratory concentrates on the role of goblet cell mucin production in health and in the inflammatory disease
allergic conjunctivitis. The specialized pro-resolving molecules (SPMs) are produced from omega-3 fatty acids
such as DHA. There is a complex and tightly regulated biology of using pro-resolution molecules to control
goblet cell mucin secretion and maintain ocular surface homeostasis. In disease there is an allergy-mediated
dysregulation/overproduction of mucins that contribute to the pathophysiology that SPMs resolve. Our overall
goal is to investigate how SPMs are produced by the conjunctiva and act in a sex-dependent manner at a
molecular level in conjunctival goblet cells to regulate mucin secretion in health and disease. We will focus on
the resolvin Ds RvD1-6 that are present in tears and conjunctiva. RvD1 and RvD2 stimulate goblet cell
function. In Specific Aim 1 we will focus on health and determine which RvD family members (RvD3-6)
increase the intracellular [Ca2+] ([Ca2+]i), elevate cAMP, and stimulate mucin secretion in cultured conjunctival
goblet cells. For this and all three aims we will evaluate if there a sex-dependent difference in response. In
Specific Aim 2 we will investigate if in health RvD1 uses an autocrine circuit with a GPR32 (receptor) /DHA
(precursor)/RvD1 axis to control its biosynthesis. In Specific Aim 3 we will study disease and in allergic
conjunctivitis interrogate which RvD family members (RvD2-6) counter pro-inflammatory mediator stimulated
goblet cell increase in [Ca2+]i and secretion, and promote resolution of AED in vivo. We will use human
cultured conjunctival goblet cells, two types of SPM receptor knock out mice, and a mouse model of allergic
eye disease. Intracellular [Ca2+], cAMP, MUC5AC secretion, DHA release, and RvD1 biosynthesis will be
measured. In the animal model clinical symptoms, MUC5AC secretion, and leukocyte trafficking will be
determined.

## Key facts

- **NIH application ID:** 9851865
- **Project number:** 5R01EY019470-11
- **Recipient organization:** SCHEPENS EYE RESEARCH INSTITUTE
- **Principal Investigator:** Darlene A Dartt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $550,751
- **Award type:** 5
- **Project period:** 2009-05-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851865

## Citation

> US National Institutes of Health, RePORTER application 9851865, Conjunctival Goblet Cell Mucin Secretion in Inflammation and Its Resolution (5R01EY019470-11). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851865. Licensed CC0.

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