# Defining the Immune Cell Roles in Meibomian Gland Dysfunction in the Context of Ocular Surface Immune Diseases

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $398,756

## Abstract

ABSTRACT
Inflammation is a vastly underappreciated player in meibomian gland dysfunction – a common pathological
condition of eyelid sebaceous glands responsible for producing tear film lipids. Pathologic blockage of the gland
orifice and central duct, referred to as “obstructive” meibomian gland dysfunction, is regularly accompanied by
ocular surface inflammation in patients. Moreover, this type of obstruction is ubiquitous, and even more
aggressive, in patients with ocular surface immune disease. The latter is defined here as ocular surface
pathology associated with systemic immune disorders, such as atopy (allergy), Stevens-Johnson syndrome/toxic
epidermal necrolysis, Sjogren’s syndrome, graft versus host disease, cicatricial pemphigoid, and others. Still,
the exact immune mechanisms involved in meibomian gland dysfunction remain elusive. As no pharmacological
agents are indicated for meibomian gland dysfunction, there is a critical need for uncovering the pertinent
immune responses of this pathobiology in patients with ocular surface immune disease. In the last funding cycle,
we showed a direct role for neutrophils in meibomian gland dysfunction in our model of chronic-like allergic eye
disease. Based on this work and the current literature, our central hypothesis is that neutrophils play a role in
driving meibomian gland dysfunction across different forms of ocular surface immune diseases. In the current
proposal, we will: i) elucidate the pathogenic neutrophil mechanisms that drive meibomian gland dysfunction in
our established model of chronic-like allergic eye disease; ii) decipher the role of neutrophils in meibomian gland
dysfunction in a novel and spontaneous genetic mouse model of ocular surface immune disease; and iii) map
the tear immune cell landscape of meibomian gland dysfunction in patients with different ocular surface immune
disease entities. In addition to mouse models, we will leverage our unpublished single cell RNA-seq dataset of
immune cells from blood, conjunctiva, and tears from our allergic eye disease mouse model, paired with
computational, genetic, and pharmacologic tools to pinpoint the pathogenic neutrophil mechanisms. For human
samples, we established a 36-color flow cytometry panel for deep immune profiling of patient tears and have
incorporated clinical expertise for the annotation of each individual with detailed clinical metadata. The rationale
for this project is that identifying the critical immune cell subsets and associated pathogenic cellular programs
that drive meibomian gland dysfunction will offer a strong scientific framework by which to delineate the role of
inflammation in human meibomian gland dysfunction, as well as identify novel therapeutic targets and diagnostic
immune markers to support efforts in the clinical space. Completion of these studies is therefore expected to
have a significant impact by expanding the breadth and depth of knowledge regarding the role of inflammation,
specifically neu...

## Key facts

- **NIH application ID:** 10519089
- **Project number:** 2R01EY021798-11
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Daniel Raphael Saban
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $398,756
- **Award type:** 2
- **Project period:** 2012-02-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10519089

## Citation

> US National Institutes of Health, RePORTER application 10519089, Defining the Immune Cell Roles in Meibomian Gland Dysfunction in the Context of Ocular Surface Immune Diseases (2R01EY021798-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10519089. Licensed CC0.

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