# Pathobiology of autoimmune Meibomian gland dysfunction

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2024 · $251,250

## Abstract

Dry eye disease (DED) is a chronic condition affecting millions worldwide, with approximately 21 million
patients affected in the US. Symptoms of DED vary from mild irritation to severe ocular pain, and, if left untreated,
can lead to the loss of vision. The pathogenesis of DED is a subject of intense research efforts, but its etiology
is still unknown. It can be classified as evaporative dry eye (which includes Meibomian Gland Dysfunction [MGD])
and aqueous-tear-deficient DED (which includes lacrimal gland deficiencies, such as Sjögren Syndrome [SS]).
Meibomian glands (MGs) secrete lipids (meibum) onto the ocular surface to stabilize the tear film. Changes in
MG function (MGD) lead to altered quality and quantity of meibum, causing increased tear film evaporation, and
leading to evaporative DED. Clinical studies suggest that 85% of all DED cases are caused by some form of
MGD. Despite the high prevalence of MGD, its etiology has not been fully investigated. SS is an autoimmune
DED characterized by over-reactive CD4+T cell-mediated inflammatory response in various tissues. Studies
have demonstrated that a high prevalence of SS patients present MGD. However, the pathobiology of MGD in
SS patients remains unknown. Our innovative hypothesis is that SS patients also present an autoimmune
response in the MG that leads to an autoimmune form of MGD. This hypothesis is supported by our preliminary
studies showing that CD25KO mice, a mouse model of SS rich in autoreactive T cells and no regulatory T cells
(Tregs), present CD4+T cell infiltration in the MG area, which is associated with MG atrophy and drop-out.
Further, the co-adoptive transfer of CD4+T cells from CD25KO mice into immune-deficient mice leads to immune
cell infiltration into the MG, causing MGD. Interestingly, the co-adoptive transfer of wild-type Tregs with CD4+T
cells from CD25KO mice is enough to prevent immune cell infiltration in the MG and MGD. Based on this
preliminary data, we hypothesize that autoreactive CD4+T cell infiltration into the MG area drives MG damage,
causing MGD. Taken together, this proposal will characterize the inflammatory cell infiltration into the MG area
in two well-established murine models of SS, and thereafter establish how autoimmune CD4+T cells are able to
lead to MG damage, causing an autoimmune form of MGD. This will be accomplished with the following specific
aims: Specific Aim 1: To characterize the MG inflammatory cell infiltration in the MG of CD25KO mice and
how it contributes to MGD; and Specific Aim 2: Investigate if autoimmune CD4+ T cells can cause MGD
and whether this can be prevented by Tregs. Currently, the etiology of MGD remains elusive, and, thus, it is
difficult to design preventative therapies and treatments. Understanding and characterizing a potential role for
inflammation (particularly CD4+T cell) in MGD will open new research avenues for developing new treatments.
This work is significant because it will develop and characterize for t...

## Key facts

- **NIH application ID:** 10992534
- **Project number:** 1R21EY036677-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Vivien Jane Coulson-Thomas
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $251,250
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10992534

## Citation

> US National Institutes of Health, RePORTER application 10992534, Pathobiology of autoimmune Meibomian gland dysfunction (1R21EY036677-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10992534. Licensed CC0.

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