# Molecular mechanisms of corneal recurrent erosion formation

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2020 · $565,266

## Abstract

Corneal surface injuries are painful and expose the eye to infections that can destroy vision. During our
previous funding period, we characterized a model for the study of recurrent corneal erosions in mice and
showed that subbasal nerves (SBNs) fail to reinnervate the cornea prior to erosion formation. In addition, we
showed that we could induce SBN reinnervation by treating debridement wounded corneas with mitomycin C
(MMC). The long-term goal of our research is to identify the factors that prevent the corneal epithelium from
reforming an intact stable barrier after trauma. One factor is failed reinnervation of the SBNs. Our data lead us
to propose two hypotheses. The first (Aim A) is that corneal epithelial basal cells adhere to, protect,
organize, and maintain the subbasal nerves (SBNs) that originate from the trigeminal ganglion. The corneal
epithelial cells protect individual SBNs by secreting a laminin-rich ECM to insulate them from one another,
organize SBNs by enclosing clusters of several SBNs within infoldings of their basal and basolateral cell
membranes forming epithelial cell:axon adhesions, and maintain optimal SBN function by removing damaged
SBN stubs during homeostasis and after injury by phagocytosis. We will test this hypothesis by conducting
experiments to answer the following questions: 1. Do corneal epithelial cells adhere to and provide support to
SBNs using adhesion complexes and proteins similar to those used by non-myelinating Schwann cells? 2. Do
corneal epithelial cells phagocytose axonal debris during homeostasis and in response to SBN damage? 3. Do
corneal epithelial cells respond to SBN denervation by altering expression of genes that regulate axon
regeneration in Schwann cells? A second hypothesis (Aim B) proposed is to resolve corneal pathology after
trauma or disease, adhesion between corneal epithelial cells, SBNs, and the basement membrane must
be restored to levels present prior to development of pathology. This hypothesis is supported by
preliminary data showing that MMC reduces corneal epithelial cell migration in vitro and MMP9 expression in
vivo. We will test this hypothesis by conducting experiments to answer the following questions: 1. Do corneal
epithelial cells at the center of the wounded mouse cornea undergo senescence? 2. Can reinnervation be
accelerated by treating crush (trephine only) wounded corneas with MMC? 3. Can erosions be eliminated after
they form by treating mouse corneas with MMC? 4. Can MMC improve reinnervation of corneas in mice with
dry eye disease? 5. Does a prior injury (conditioning lesion) improve reinnervation after crush or debridement
wounds? Comparing reinnervation after different wound types allows us to differentiate between mechanisms
that permit reinnervation after crush wounds from those that prevent reinnervation after debridement wounds
and will give us insight into how MMC enhances reinnervation.

## Key facts

- **NIH application ID:** 10011804
- **Project number:** 5R01EY008512-31
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Mary Ann Stepp
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $565,266
- **Award type:** 5
- **Project period:** 1992-07-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011804

## Citation

> US National Institutes of Health, RePORTER application 10011804, Molecular mechanisms of corneal recurrent erosion formation (5R01EY008512-31). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10011804. Licensed CC0.

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