# Epithelial stem cells in Meibomian gland development and homeostasis

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $410,000

## Abstract

Project Summary
Dry eye disease (DED), which occurs when there is inadequate lubrication of the eyes due to insufficient tears
or excessive tear evaporation, affects over 16 million adults in the U.S., and the prevalence continues to increase.
If left untreated, DED can lead to serious problems including inflammation of the eye, corneal abrasions, and
even vision loss. While DED can be due to a variety of causes, ~90% of cases are due to Meibomian gland
dysfunction (MGD). The Meibomian glands (MGs) are holocrine sebaceous glands located in the eyelids.
Differentiated meibocytes within the MGs secrete meibum, a mixture of lipids and proteins that coats the ocular
surface and prevents tear evaporation. MGD can be due to reduced meibum secretion, resulting from abnormal
MG activity, blockage of the MG orifice due to hyper-keratinization, or structural defects such as MG atrophy or
dropout. Another possible cause of MGD is stem cell exhaustion, in which MG resident stem cells are unable to
replenish meibocytes due to dysregulated stem cell differentiation. MG development is well-conserved in mice
and humans. In mice, MGs begin to develop at embryonic day 18.5 from the ectodermal epithelium; the MG
anlage grows out of the eyelid mesenchyme, elongates, branches, and differentiates into ductules that form the
acini; one MG contains clusters of these secretory acini which contain the meibocytes. MGs are fully formed by
postnatal day 15. Throughout life, meibocytes are replenished from a stem cell population within the acini. While
MG morphological development has been well described, the identity of the stem cell population(s) that gives
rise to the MG remains controversial. Additionally, the resident stem cell population responsible for replenishing
meibocytes after holocrine secretion in mature MG has not been definitively identified. Previous studies indicate
there is a limited number of precursor meibocytes, which may be the cause of stem cell exhaustion that can
occur with aging. Thus, the stem cell origin(s) and molecular mechanisms underlying MG development and
homeostasis, i.e. replacement of acinar meibocytes throughout life, remain major knowledge gaps in the field.
 A recent study from our laboratory identified Krox20 as a marker of a stem cell population in the hair follicle
that differentiates into hair shaft progenitor cells in the hair matrix, and ultimately constitutes the structural
component of the hair shaft (Liao, G&D, 2017). Follow-up preliminary studies revealed that a population of
Krox20+ cells also gives rise to the MG and depletion of these Krox20+ cells or the KROX20 protein results in
lack of MGs. These data highlight a critical role for Krox20 in MG development. We hypothesize that Krox20
marks a novel stem cell population that gives rise to the MG. Our objectives in this proposal are to investigate
the role of these Krox20+ cells in MG morphogenesis and homeostasis, and delineate the mechanisms by which
KROX20 exerts its bio...

## Key facts

- **NIH application ID:** 10341666
- **Project number:** 1R01EY033344-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Lu Le
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $410,000
- **Award type:** 1
- **Project period:** 2022-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10341666

## Citation

> US National Institutes of Health, RePORTER application 10341666, Epithelial stem cells in Meibomian gland development and homeostasis (1R01EY033344-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10341666. Licensed CC0.

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