# Effects of cornea epithelial barrier disruption on the cornea trigeminal neural circuit

> **NIH NIH U01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $1,187,390

## Abstract

Abstract
This proposal investigates the cornea-trigeminal neural circuit with particular emphasis on the
relationship between the cornea epithelium and the intraepithelial nerves to investigate the
hypothesis that ocular surface pathologies that involve transient and/or prolonged corneal
epithelial barrier disruption will cause greater nociceptor stimulation, discomfort, pain and a
compensatory reduction in epithelial and stromal nerve density. Single cell RNA and epigenetic
profiling and in situ hybridization will be performed in corneal and trigeminal ganglion cells that
project to the cornea in homeostatic conditions and after epithelial barrier disruption due to dry
eye and corneal epithelial debridement. Data from these assays will be integrated and single cell
atlases of the cornea and trigeminal ganglion under normal and stressed conditions will generated
that identify cells based on unique expression profiles. Cells will be spatially resolved in these
tissues to identify communications between corneal cells and nerve axons and between trigeminal
neuronal and non-neuronal cells. In the ganglion, temporally and spatially resolved transcriptomic
data will be associated with the changes in corneal epithelial nerve morphology and sensitivity
that occur after barrier disruption to identify genes that maintain the corneal epithelial nerves in
health and promote the pathological changes after barrier disruption. Three specific aims are
proposed to investigate the cornea-trigeminal circuit. Aim 1 will investigate the effects of barrier
disruption from dry eye and epithelial debridement on transcriptomic profiles, corneal epithelial
nerve morphology and nerve function. Aim 2 will investigate the effects of preserving epithelial
barrier in the MMP-9 knockout strain in dry eye and epithelial wounding on these parameters, and
Aim 3 will investigate the effects of two neural sensitizing chemokines on the circuit in normal and
dry eyes.
The proposed experiments investigate the cornea epithelial-trigeminal sensory circuit at a
coordinated deep level to identify factors that impact the intraepithelial nerves in health and
disease. At the conclusion of this project, we will have a better understanding of the mechanisms
by which corneal epithelial cells and intact barrier suppress nerve activation and the factors
produced by cornea cells in barrier disrupted corneas that cause nerve degeneration and
heightened sensitivity. The benchmark accomplishments of this project will be a fundamental
new understanding of the impact of corneal epithelial barrier disruption that occurs in common
corneal diseases on the integrity and function of the corneal epithelial nerve network.

## Key facts

- **NIH application ID:** 10913525
- **Project number:** 5U01EY034692-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** RUI CHEN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,187,390
- **Award type:** 5
- **Project period:** 2022-09-30 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913525

## Citation

> US National Institutes of Health, RePORTER application 10913525, Effects of cornea epithelial barrier disruption on the cornea trigeminal neural circuit (5U01EY034692-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10913525. Licensed CC0.

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