# Defining Corneal Schwann cells in Injury

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $205,000

## Abstract

The transparent cornea is a highly innervated tissue and sustains significant nerve damage during
common procedures such as corneal transplantation and vision correction. Unfortunately, the
restoration of corneal sensory function after damage is usually inadequate due to aberrant and poor
regeneration of axons. In vascularized tissues, such as the sciatic nerve and spinal cord Schwann
cells (SCs) are known to support axonal regeneration after injury. However, little is known how
corneal SCs respond to injury or surgical procedures as this cell types has not previously been
investigated. Studies performed in sciatic injury models reveal that both the genetic encoded
factors of SCs, as well as the extracellular matrix components govern the axonal repair process.
The dedifferentiation of SCs into a repair SCs – a transient cell type – that re-differentiates into a
terminal SC is a hallmark of SC-driven mechanisms in axonal regeneration. In the cornea, the bulk
of sensory axons are unmyelinated axons, except at the limbus where they are myelinated. It is
presumed that lesions of nonmyelinating corneal axons also enlist the support of their respective
SCs for axonal regeneration, mirroring similar activities of SCs of injured vascularized tissues.
This idea has not been formally tested before, as experimental evidence to support or refute this
paradigm is lacking. To learn what genes are expressed specifically in corneal SCs, we performed
a single cell RNA sequence analysis of the rabbit cornea and identified the corneal SC
transcriptome. With cross-species validation of several SC-specific target proteins in mouse
corneas and validation of a transgenic mouse line expressing proteolipid protein 1-enhanced green
fluorescent protein (Plp1-eGFP), we demonstrated SC-specific reporter gene expression in vivo.
In this exploratory R21 grant, we propose two aims. In specific aim 1, we will exploit the Plp1-
eGFP reporter transgenic line in a corneal stromal injury model causing nerve severance and
investigate corneal SC to myofibroblast differentiation over the course of axonal degeneration and
repair. These studies will help define whether corneal SCs differentiate into myofibroblasts and
nature of injury that promotes this aberrant phenotype. In specific aim 2, we will investigate the
wingless (Wnt) signaling pathway in corneal SCs, as molecular components of this pathway
showed differential high expression in SCs compared to other corneal cells. We plan to investigate
how modulation of the Wnt inhibitor Dickkopf-1 (Dkk1) governs corneal axonal regeneration after
injury and effects on corneal mechanical sensation. Together, these objectives will help to lay
down the foundation to identify novel targets for SC-therapeutics towards improvement of corneal
axonal growth and sensory impairment.

## Key facts

- **NIH application ID:** 10129070
- **Project number:** 1R21EY031113-01A1
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** ROYCE MOHAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $205,000
- **Award type:** 1
- **Project period:** 2020-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129070

## Citation

> US National Institutes of Health, RePORTER application 10129070, Defining Corneal Schwann cells in Injury (1R21EY031113-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10129070. Licensed CC0.

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