# Phosphatidylglycerol as a Therapy for Corneal Injury

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2021 · $373,450

## Abstract

Project Summary/Abstract
 Corneal wounds and abrasions occurring as a result of injury, chemical burns, surgery, contact lens wear
and dry eye syndrome are painful and can predispose individuals to infection. Although these wounds tend to
heal rapidly, in some cases, such as in diabetes, the healing may be delayed or may even fail; in other cases
individuals may continue to show persistent or chronic inflammation despite resolution of the injury or infection.
This persistent sterile inflammation can interfere with corneal clarity thereby compromising vision; therefore,
treatments to inhibit inflammation while improving corneal wound healing are needed. In exciting novel results
we have found that a naturally occurring phospholipid, dioleoylphosphatidylglycerol (DOPG), enhances corneal
epithelial wound healing in wild-type mice and in an experimental mouse model of impaired corneal wound
healing in vivo. These data suggest the possibility of using DOPG to enhance corneal wound healing
therapeutically. Information in the literature also supports a potential role for DOPG in suppressing
inflammation. Thus, we have recently demonstrated that DOPG suppresses skin inflammation by inhibiting the
activation of pattern recognition receptors, such as toll-like receptor-2 (TLR2) and toll-like receptor-4 (TLR4), in
response to damage-associated molecular patterns (DAMPs), endogenous molecules released from injured
cells to alert the innate immune system to the presence of danger so that a protective immune response can
be mounted. Indeed, a recent article examining an in vivo rodent model of sterile inflammation demonstrated
that heat shock protein B4 (HSPB4, also known as crystallin Alpha A) released from corneal keratocytes in
response to damaged corneal epithelial cells serves as a DAMP to activate TLR2 on corneal macrophages and
induce corneal inflammation. In innovative preliminary studies we have found that DOPG can inhibit
macrophage inflammatory mediator production in response to HSPB4, suggesting the likelihood that this lipid
will suppress this corneal inflammation. Based on our preliminary results, we hypothesize that DOPG will act
not only to accelerate corneal wound healing but also to suppress inflammation by inhibiting TLR2 and/or TLR4
activation. In the research proposed, we will test the idea that DOPG will: (1) dose-dependently, safely and
physiologically accelerate corneal epithelial wound healing without adverse effects, at an optimal dose to be
determined, in normal and diabetes-impaired corneal wound healing mouse models, and (2) inhibit neutrophil
infiltration and inflammation in in vivo mouse models of corneal injury through its ability to inhibit TLR2/4
activation. In a third aim we will also determine the mechanism by which DOPG exerts these effects to
stimulate corneal epithelial wound healing and inhibit TLR2/4 activation and inflammation. If our hypothesis
proves correct, it would suggest the possibility of developing DOPG as a s...

## Key facts

- **NIH application ID:** 10179401
- **Project number:** 5R01EY030576-03
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Wendy B Bollag
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $373,450
- **Award type:** 5
- **Project period:** 2019-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179401

## Citation

> US National Institutes of Health, RePORTER application 10179401, Phosphatidylglycerol as a Therapy for Corneal Injury (5R01EY030576-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10179401. Licensed CC0.

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