# Molecular Generators at Corneal Wounds Produce and regulate the Wound Electrical Signals

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $392,500

## Abstract

Abstract (Description)
Live and intact cornea maintains an electric potential difference across the epithelium, the transepithelial
potential difference (TEP). The compromised epithelial barrier in corneal wounds collapses the
transepithelial potential at the wound site, resulting in naturally occurring endogenous electric fields that
point towards the wound center from adjacent intact tissues. These naturally occurring wound electric
fields (wEFs) provide powerful signals that stimulate and guide cells to migrate into the wound to initiate
healing. We demonstrated that these electrical signals could override other directional cues, such as
injury stimulation, free edge and mechanical forces, in guiding migration of corneal epithelial sheets and
large groups of cells. Our long term goal is to elucidate the molecular mechanisms that generate and
regulate the wound electric fields, i.e. to discover the “molecular generators”, and to use this knowledge
to develop new therapeutic strategies to collectively mobilize cells (tissues) to heal chronic wounds and
non-healing wounds. Our previous research has identified key ionic mechanisms and “molecular
generators” that produce and regulate wEFs. Importantly, we demonstrated in three diabetic models that
wEFs are defective and this correlates very well with impaired healing. Using high throughput screens,
we also identified novel molecular mechanisms directing the responses of human corneal epithelial cells
(CECs) to physiological electric fields. In this application, we will dissect the defective electrical signaling
and impaired responses of epithelial cells in diabetic cornea. We therefore propose a comprehensive
study to (1) elucidate ionic mechanisms underlying defective electrical signaling in diabetic corneal
wounds, and to build a mathematical model that simulates wound electric fields; (2) determine how high
glucose and oxygen uptake regulate electrogenic machinery, and how these mechanisms are impaired in
diabetic cornea. Through completion of these aims, our goal is Aim (3) to electrically facilitate healing of
diabetic wounds by correcting defects in generation of electrical signals.

## Key facts

- **NIH application ID:** 9892012
- **Project number:** 5R01EY019101-10
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Min Zhao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2009-12-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892012

## Citation

> US National Institutes of Health, RePORTER application 9892012, Molecular Generators at Corneal Wounds Produce and regulate the Wound Electrical Signals (5R01EY019101-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9892012. Licensed CC0.

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