# Immunopathogenic mechanisms of dry eye disease

> **NIH NIH R01** · SCHEPENS EYE RESEARCH INSTITUTE · 2020 · $124,896

## Abstract

Dry eye disease (DED) is a chronic immune-mediated disorder of the ocular surface, characterized by
disruption of the epithelial barrier and sustained ocular surface inflammation, which in severe cases results
in blindness from corneal ulceration and scarring. DED is arguably the most common ophthalmologic
condition for which patients visit eye care professionals, with more than 16 million US adults estimated to
have been diagnosed with DED (several folds higher than age-related macular degeneration). Notably, the
prevalence of DED increases with age. The financial burden of DED to the US healthcare system is vast,
with direct costs and expenses from productivity losses estimated to exceed $3.5 billion annually.
 The work of several laboratories, including the Principal Investigator's, has revealed key insights
concerning the immunopathogenesis of DED. There is now strong evidence that T helper-17 (Th17) cells
are critical promoters of immune-mediated damage to the ocular surface. The PI's laboratory has shown
that memory Th17 (mTh17) cells maintain disease chronicity, resulting in ocular surface epitheliopathy that
persists for many months after exposure to desiccating stress. Moreover, data from the PI's lab show that
regulatory T cells (Tregs) are defective in suppressing the Th17 response in DED. In addition, the PI's lab
has identified critical mechanisms controlling antigen-presenting cell (APC) activation and trafficking in
DED, as well as effector Th17 priming, expansion and homing. Despite substantial progress in unraveling
underlying immunopathogenic mechanisms, important questions remain unanswered.
 We hypothesize that (1) chronic DED is characterized by long-term impairment in the function of
regulatory T cells (Tregs) that normally maintain immune quiescence, and that (2) the aged are more
susceptible to DED due to a larger pool of memory Th17, whose function is inadequately regulated by aged
Tregs. The principal objectives of this project are to (i) precisely define the phenotypic changes that
characterize, and the mechanisms that promote long-term Treg dysfunction in DED; (ii) determine the
cellular precursors of mTh17 cells, as well as the cytokine mechanisms that influence the generation of
immunologic memory; and (iii) define the factors that amplify mTh17 immunity in aging. To achieve these
objectives, three specific aims have been defined to answer the following questions: Aim 1: What are the
causative mechanisms of enduring Treg dysfunction in DED? Aim 2: Which effector Th17 subsets are
predisposed to enter the memory pool (thus permitting DED chronicity), and what factors regulate this
process? And finally Aim 3: What are the cellular and molecular mechanisms that augment Th17-mediated
DED in aging? It is anticipated that this research will have significant translational impact given the high
prevalence of DED, the still limited knowledge we have regarding its immunopathogenesis, and the relative
scarcity of effective treat...

## Key facts

- **NIH application ID:** 10197402
- **Project number:** 3R01EY020889-10A1S1
- **Recipient organization:** SCHEPENS EYE RESEARCH INSTITUTE
- **Principal Investigator:** Reza Dana
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $124,896
- **Award type:** 3
- **Project period:** 2010-09-30 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197402

## Citation

> US National Institutes of Health, RePORTER application 10197402, Immunopathogenic mechanisms of dry eye disease (3R01EY020889-10A1S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10197402. Licensed CC0.

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