# Molecular mechanisms of corneal recurrent erosion formation

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2022 · $671,689

## Abstract

Project Summary/Abstract (max. 30 lines)
Loss of corneal sensory nerves develops secondary to herpes infections, stroke, or trauma; treatments are
often only partially successful and lead to suffering and vision loss. The long-term objective of our research is
to identify the factors that permit the corneal epithelium to reform a stable barrier after trauma so we can
intervene to prevent corneal erosions from forming. Our studies of the cornea have recently focused on the
intraepithelial corneal sensory nerves (ICNs) which consist of the intraepithelial corneal basal nerves (ICBNs)
and the intraepithelial corneal nerve terminals (ICNTs). Mitomycin C (MMC) applied topically at the time of
debridement injury acts as a neuroprotective agent. Corneal epithelial and resident dendritic cells phagocytose
axonal mitochondria (aMito) from severed axons after injury. Apical cell desquamation, ICN growth and ICNT
shedding are under diurnal control. We hypothesize that the ocular surface barrier and the extent of corneal
tissue damage in response to injury and irritants varies with the time of day. We will test this hypothesis in Aim
A by answering the following questions: 1. Does shedding of the ICNTs and the desquamation of squames
occur spontaneously when lights turn on or does it persist in the dark? 2. Do differences in the corneal barrier
and ICN density in the resting and active phase in the mouse impact the extent of damage done to the cornea
and signaling by the ICNs to the trigeminal ganglion in response to injury and after exposure to ocular irritants
The daily shedding and severing the ICNs leads to accumulation of aMito within corneal epithelial cell
lysosomes followed by their degradation via transmitophagy; by contrast to retinal pigment epithelial (RPE)
cells, the mechanisms that regulate phagocytosis of axonal debris in the corneal epithelium are not known.
Data from our lab and others lead us to hypothesize that corneal epithelial cells internalize aMito via LC3B
associated phagocytosis (LAP) and, after internalization, corneal epithelial cells regulate whether aMito
undergo transmitophagy or are retained in their cytoplasm to function metabolically. We test this hypothesis in
Aim B by answering the following questions: 1. Is phagocytosis of aMito and severed axons by corneal
epithelial cells mediated by LAP? 2. Are functional aMito retained in the cytoplasm of epithelial cells after being
transferred from axons into corneal epithelial cells during homeostasis and in response to injury?
The experiments proposed use quantitative in vitro and in vivo cellular and molecular approaches to answer
these questions. The knowledge gained from these studies will not only inform clinicians about the optimal time
of day to deliver treatments for ocular surface disorders, they will also clarify the role that mitochondrial transfer
has on enhancing wound recovery after injury in the cornea.

## Key facts

- **NIH application ID:** 10466910
- **Project number:** 5R01EY008512-33
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Mary Ann Stepp
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $671,689
- **Award type:** 5
- **Project period:** 1992-07-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10466910

## Citation

> US National Institutes of Health, RePORTER application 10466910, Molecular mechanisms of corneal recurrent erosion formation (5R01EY008512-33). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10466910. Licensed CC0.

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