# Calcium oscillations and cell motility with corneal injury

> **NIH NIH R21** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $206,250

## Abstract

According to the World Health Organization, corneal blindness from disease and injury is one of the top
causes of blindness. Diabetes increases the risk of improper wound repair after minor scratches, corneal
transplantation, and removal of epithelium during vitrectomy or refractive surgery. Altered focal adhesion,
hemidesmosome, and cell-cell junction dynamics are common hallmarks of poor wound healing. Our group
has demonstrated increased expression of the ATP-binding purinoreceptor, P2X7 in human diabetic
corneas and in a murine model of Type II diabetes (DIO) accompanied by impaired wound healing.
Furthermore, changes in P2X7 alters focal adhesion turnover and actin bundling in vitro that may lead to
impaired wound healing. We have preliminary data from both wounded corneal epithelial cultures and
explants demonstrating that sustained calcium oscillations occur after stimulation and travel between cells
for hours. We found that when calcium mobilizations were absent between cells at the leading edge, that
lamellipodial protrusions were absent. It is not known which receptor is required for this activity; however,
we predict that the oscillations are a result of a highly-orchestrated activation of purinoreceptors. Previously
we demonstrated that knockdown of specific purinoreceptors altered downstream signaling pathways that
involve cell motility and adhesion proteins.
 Our goal in this innovative proposal is to use image processing and machine learning to
understand the events that occur in cell-cell communication that induce cell migration in corneal epithelia
and to examine how these events are mediated in corneas from a diabetic induced obesity murine model.
The proposal challenges the accepted paradigm that the cell-cell communication wave in the wounded
cornea is a short-lived on-and-off signal, but that it is a prolonged oscillating signal needed for healthy
epithelial cell migration to effectively heal the wounded cornea. As the calcium and motility assays yield
large data sets and complex patterns, we are collaborating with a neuroscientist and a computer scientist
to utilize machine learning to determine when cells will interact if specific receptors or complexes of
receptors are activated. To address these questions, we will simultaneously perform live cell imaging of
calcium mobilization, actin and ATP release in epithelium of wounded corneas under normal and diabetic
conditions. The aims are: 1. To determine if there are specific response signatures elicited by the
sustained calcium mobilizations and signaling generated with injury in control corneas and
corneas from diet induced obesity mice; and 2. To determine if the intercellular calcium
mobilizations required for the initiation of lamellipodial ruffling are necessary for proper
migration?

## Key facts

- **NIH application ID:** 9853790
- **Project number:** 5R21EY029097-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Vickery E Trinkaus-Randall
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $206,250
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853790

## Citation

> US National Institutes of Health, RePORTER application 9853790, Calcium oscillations and cell motility with corneal injury (5R21EY029097-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9853790. Licensed CC0.

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