# Lipid mediators and their signaling in ocular surface inflammation and meibomian gland dysfunction

> **NIH VA I01** · MIAMI VA HEALTH CARE SYSTEM · 2021 · —

## Abstract

Dry eye (DE) affects 1 in 5 veterans and impacts quality of life. It is a complex disease that manifests with
multiple symptoms (e.g. pain, visual disturbance) and signs (e.g. decreased tear production, increased
evaporation). Key pathophysiological components of DE are ocular surface inflammation and meibomian gland
dysfunction (MGD). Despite its frequency and morbidity, current therapies do not relieve symptoms in all
patients. In order to appropriately manage DE, it is necessary to understand mechanisms and specific
contributors to disease sub-types. The overall goal of this proposal is to improve such knowledge by studying
the role of bioactive sphingolipids (SPL) in MGD and other aspects of DE. Our preliminary and published
work suggest SPL composition changes (higher sphingomyelin (SM)/ ceramide (Cer) ratio) in poor quality
meibomian gland secretion (meibum); a higher ratio of pro-inflammatory (ω-6) /pro-resolving (ω-3) lipids, and
higher levels of prostaglandin E2 in tears from DE patients. Bioactive Cer generated from SM by
sphingomyelinases (SMase) and its derivatives, ceramide 1-phosphate and sphingosine 1-phosphate are
inflammatory lipids and can induce formation of other inflammatory lipids such as prostaglandins. We detected
SMase activity in human tears. In this proposal, we will test the hypothesis that changes in SPL composition in
meibum contribute to various signs of DE including ocular surface inflammation, tear film disturbances, and
MGD. In Aim 1, we will profile meibum and tear SPL and pro- and anti-inflammatory PUFAs and eicosanoids
by LC-MS/MS from 120 cases (poor meibum quality) and 120 controls (normal meibum quality), chosen from
our prospectively collected samples from a large veteran population after a comprehensive eye evaluation
(mean age 62±10; 467 males, 46 females; 230 white, 272 black). Correlation and regression analysis will be
performed with clinical data as dependent variables and lipid mediators as independent variables. In Aim 2, we
will determine acitivity of SMAse (acidic and neutral) from 240 Schirmer's strips corresponding to the samples
in Aim 1. We will then build models looking at relationships between SMase activity, SPL, and ocular surface
inflammation. In Aim 3, we will identify molecular connections between SPL and inflammation in an in vitro
model by using human immortalized meibomian gland epithelial cell line (HMGEC) to test the effects of
bioactive SPL on mediating inflammation, cell viability, cell death etc. in normal and hyperosmolar conditions.
Impact: Our results will identify SPL differences by MGD status, elucidate relationships between bioactive
SPL, inflammatory lipid mediators, and SMase activity with ocular surface inflammation and clinical features of
MGD and DE sub-types. The knowledge generated will advance the field by determining the relative
contributions of different lipids on different manifestations of DE and provide the foundation for developing new
molecular targets for...

## Key facts

- **NIH application ID:** 10013711
- **Project number:** 1I01BX004893-01A1
- **Recipient organization:** MIAMI VA HEALTH CARE SYSTEM
- **Principal Investigator:** Anat Galor
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013711

## Citation

> US National Institutes of Health, RePORTER application 10013711, Lipid mediators and their signaling in ocular surface inflammation and meibomian gland dysfunction (1I01BX004893-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10013711. Licensed CC0.

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