# The Role of Sustained Calcium Oscillations in the Wound Healing Response

> **NIH NIH F30** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $50,520

## Abstract

PROJECT ABSTRACT
The cornea is the most anterior structure of the eye, which makes it susceptible to injury from scratching,
infections, and dystrophy. In fact, corneal blindness from injury and disease is the fourth highest cause of
preventable blindness globally. The only curative treatment for this condition is corneal transplantation or
grafting, but viable eye tissues are not readily available worldwide. Therefore, studying the mechanism of
normal wound healing in the cornea could give us information on development of potential novel therapeutic
targets. Upon injury, corneal epithelial cells release nucleotides (e.g. ATP) that activate purinergic receptors
P2Y2 and P2X7; P2Y2 is a G-protein coupled receptor, while P2X7 is a ligand-gated ion channel. Both of
these receptors induce a transient calcium wave that has been established to be a critical step in the wound
healing process. However, little is known about the long-term role of calcium signaling in wound repair. Given
that the expression and localization of P2X7 and P2Y2 change after the initial calcium wave, we speculated
that these receptors may also be involved in the later stages of the wound healing process. We have now
identified a long-term role of calcium propagation that when inhibited attenuates the healing process. This
secondary response, which occurs 10-30 minutes after the primary calcium wave is induced, consists of a
series of calcium oscillations that propagate within multiple clusters of cells, and it was seen to last for several
hours. Deactivating extracellular nucleotides with ectonucleotidases inhibited the secondary response,
indicating that P2Y2 and P2X7 are required in this process. Unlike the primary response, the secondary
calcium response depended on cell-cell contact and thus was inhibited by sub-confluent conditions and gap
junction inhibitors. These results demonstrate that the calcium response after wounding is more complex than
that of either receptor alone. The goal of my project is to investigate how the purinergic receptors P2X7
and P2Y2 coordinate and produce the secondary calcium response and how that response contributes
to the wound healing process. Therefore, I hypothesize that purinergic receptors P2X7 and P2Y2
differentially mediate the secondary calcium response and contribute to multiple processes in wound repair.

## Key facts

- **NIH application ID:** 9994311
- **Project number:** 5F30EY028001-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Yoonjoo Katherine Lee
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994311

## Citation

> US National Institutes of Health, RePORTER application 9994311, The Role of Sustained Calcium Oscillations in the Wound Healing Response (5F30EY028001-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9994311. Licensed CC0.

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