# The role of the intestinal microbiota in ocular surface health

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $246,000

## Abstract

PROJECT SUMMARY
Dry eye disease (DED) is a chronic, prevalent, debilitating condition. DED is one of the most common reasons
that patients seek advice from eye care practitioners. To date, there are no cures for DED. Treatment is
palliative, focused on stabilization of the tear fluid and a reduction in ocular surface inflammation. Despite the
widespread use of topical anti-inflammatory and immunomodulatory agents for DED, treatment efficacy
remains low.
The intestinal microbiota has recently been identified as an important contributor to ocular surface health in
DED. The induction of intestinal dysbiosis has been associated with ocular surface inflammation, defects in
corneal epithelial barrier function, and alterations in corneal development and wound healing. Emerging
evidence suggests that a unique relationship exists between the intestinal microbiota and metabolic
homeostasis. Further, mitochondrial dysfunction triggered by intestinal dysbiosis may amplify the immune
response and decrease tissue responsiveness to anti-inflammatory and immunomodulatory agents.
Recent work in our laboratory has shown that corneal epithelial cells exposed to hyperosmolar stress, a
distinguishing feature of DED, exhibit distinct changes in metabolic and mitochondrial homeostasis. The goal of
this R21 proposal is to incorporate our strong background in corneal metabolism with the burgeoning field of
intestinal microbiota-linked DED. Aim 1 will determine the effects of depletion of the intestinal microbiota
on metabolic homeostasis in the corneal epithelium. Aim 2 will determine whether microbiota-
associated metabolic changes impact the sensitivity of the ocular surface to anti-inflammatory and
immunomodulatory agents. To accomplish these aims, we will use complementary animal models, primary
cell cultures, real time metabolic flux analysis, and molecular and biochemical assays that are well established
in our laboratory.
The proposed proof of concept studies are innovative and significant because they are the first studies to
investigate the relationship between the intestinal microbiota and corneal epithelial metabolism in
DED. The alleviation of mitochondrial dysfunction and microbiota-associated metabolic reprogramming in DED
may increase the responsiveness of ocular surface inflammation to anti-inflammatory and immunomodulatory
agents. This could be a game changer in how we clinically manage dry eye and offer promise to
millions of Americans that suffer from this disease.

## Key facts

- **NIH application ID:** 10362438
- **Project number:** 1R21EY033505-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** DANIELLE M. ROBERTSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $246,000
- **Award type:** 1
- **Project period:** 2021-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10362438

## Citation

> US National Institutes of Health, RePORTER application 10362438, The role of the intestinal microbiota in ocular surface health (1R21EY033505-01). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10362438. Licensed CC0.

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