# Molecular Mechanisms of corneal wound repair

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2022 · $400,125

## Abstract

According to the World Health Organization, type 2 diabetes is one of the leading pathologies that
increases the risk of improper wound healing and is now considered to be one of the leading causes of
preventable blindness. Upon injury, adjacent epithelial cells at the wound edge must communicate and
coordinate their response to move forward. Our goal in this proposal is to examine if the interactions
between P2X7 and pannexin1 are critical for homeostasis and wound repair. We have evidence that
pannexin1 mediates P2X7-induced communication and cell motility. These 2 proteins are critical for ion
mobilization, ATP transport and signaling complexes that play roles in inflammation and pain. Other
investigators have shown that P2X7 has a role in the pathogenesis of type 2 diabetes including
microvascular complications, impaired blood retinal barrier and neuropathic pain (Solini and Novak (2019).
We and our collaborators have demonstrated in corneal epithelium that: 1. P2X7 and pannexin1
localization changes with injury and is enhanced near the leading edge of control corneas; 2. Inhibition of
P2X7 diminishes communication between cells, alters components of motility and alters tyrosine
phosphorylation of focal adhesion and adaptor proteins; 4. P2X7 and pannexin1 interact in vitro and we
have preliminary data demonstrating the interaction of P2X7 and pannexin1 in control mice using proximity
ligation assays; 5. We have preliminary data that there is minimal difference in pannexin1 in unwounded
control and diabetic corneal epithelium; however the response to injury differs; and 6. Inhibition of
pannexin1 impedes cell migration in control corneas and in vitro. These led us to hypothesize that P2X7-
pannexin1 interaction in corneal epithelium is required for effective cell-cell communication and signaling
in response to injury and is needed to regulate the cytoskeleton and forces required for cell motility. The
specific aims that we will address are: determine how changes in association of purinoreceptors and
pannexin1 are regulated during corneal wound healing; determine if inhibition and/or activation of these 2
proteins changes the organization of the actin cytoskeleton and cell motility and determine if wound healing
and motility is mediated by a force exerted through the pannexin-P2X7 interaction and if it is affected by
substrate stiffness.
Our data suggest the potential for therapeutic approaches to treat delayed corneal epithelial would healing,
and recurrent corneal erosions in type 2 diabetes.

## Key facts

- **NIH application ID:** 10470861
- **Project number:** 5R01EY032079-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Vickery E Trinkaus-Randall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $400,125
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470861

## Citation

> US National Institutes of Health, RePORTER application 10470861, Molecular Mechanisms of corneal wound repair (5R01EY032079-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10470861. Licensed CC0.

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