# Age-Related Meibomian Gland Dysfunction

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $386,250

## Abstract

Project Summary/Abstract
The long-term goal of this project is to understand the mechanism of age-related meibomian gland dysfunction
(MGD) and evaporative Dry Eye EDED. Recent published studies from our laboratory using Stimulated Raman
Spectroscopy (SRS) to evaluate meibomian gland lipid quality (meibum) indicate that there is a decrease in
protein content of normal meibum within individual glands as it moves progressively from the acinus to the
orifice. This finding suggests that normal meibocyte differentiation involves removal of protein from meibum
prior to release onto the tear film. Additionally our laboratory has shown that mice exposed to low humidity
environmental stress, known to induce signs of EDED, display marked hyperproliferation of the meibomian
gland with retention of protein in the meibum lipid suggesting that environmental stress induces abnormal or
incomplete meibocyte differentiation. These findings support two alternative HYPOTHESES for the
development of MGD:1) Environmental stress or aging leads to incomplete or abnormal meibocyte
differentiation causing retention of protein in meibum, loss of lipid fluidity and inspissation. And 2)
Aging and/or repeated environmental stress leads to depletion of meibocyte stem cells and meibomian
gland dropout. These hypotheses emphasize two MAJOR GAPS in knowledge regarding meibomian gland
function: GAP1, while the lipid composition of meibum and potential hormonal and other risk factors for MGD
has been intensively studied, little is known regarding meibocyte differentiation and the cellular and molecular
mechanisms that control this process. GAP2, although the turnover rate for the meibomian gland acinar cells
has been studied, the presence of meibomian gland stem cells remains controversial and the effects of
environmental stress, aging and sex are unknown. The following Specific Aims will test our hypotheses and
explore these GAPS in knowledge: 1) Characterize using SRS the protein to lipid ratio (P/L) in expressed
meibum from human subjects exhibiting signs and symptoms of EDED and correlate P/L ratio to EDED/MGD
severity in a clinical study. 2) Identify the cellular and molecular mechanism of meibocyte differentiation and
disintegration in vitro and determine the effects of environmental stress, aging and sex on meibocyte
differentiation in vivo. 3) Identify the source of meibocyte and ductal epithelial renewal through lineage tracing
and determine the effects of environmental stress, age and sex on meibomian gland ductal epithelial and
meibocyte renewal using Confetti and the H2B-GFP/K5tTA mice and IT reconstruction.

## Key facts

- **NIH application ID:** 9969433
- **Project number:** 5R01EY021510-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** James V Jester
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,250
- **Award type:** 5
- **Project period:** 2011-09-30 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969433

## Citation

> US National Institutes of Health, RePORTER application 9969433, Age-Related Meibomian Gland Dysfunction (5R01EY021510-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9969433. Licensed CC0.

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