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Deep Corneal Nerve Plexus Selective Damage in Persistent Neurotrophic Corneal Epithelial Defects Detected by In Vivo
Seitaro Komai1,2, Manuel E Quiroga-Garza1,2, Raul E Ruiz-Lozano1,2
1Foster Center for Ocular Immunology, Duke Eye Center, Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, United States.
Investigative Ophthalmology & Visual Science
|April 1, 2025
Summary
This study reveals that benzalkonium chloride (BAK) damages corneal stromal nerves in persistent epithelial defects. An in vivo imaging system using multiphoton confocal microscopy (MCM) and CGRP:GFP Tg mice visualized this nerve damage and functional loss.
Area of Science:
- Ophthalmology
- Neuroscience
- Regenerative Medicine
Background:
- Neurotrophic corneal persistent epithelial defects (PDEs) impair corneal innervation.
- Understanding corneal nerve damage is crucial for developing effective treatments.
Purpose of the Study:
- To investigate corneal nerve damage in neurotrophic corneal PDEs.
- To utilize an in vivo imaging system with multiphoton confocal microscopy (MCM) and calcitonin gene-related peptide (CGRP):GFP transgenic (Tg) mice.
Main Methods:
- Corneal epithelial defects were induced using benzalkonium chloride (BAK).
- Wound closure was monitored, and corneal nerves were imaged in vivo using MCM.
- Three-dimensional (3D) reconstruction of CGRP-positive nerves and corneal mechanosensation were analyzed.
Main Results:
- BAK treatment significantly delayed wound closure.
- In vivo MCM successfully visualized CGRP-positive corneal nerves in 3D.
- BAK-impaired eyes showed reduced stromal nerve volume and mechanosensation.
Conclusions:
- The developed in vivo imaging system allows longitudinal observation of murine corneal nerves.
- Corneal stromal nerves are selectively damaged in persistent neurotrophic corneal epithelial defects.
- This system holds potential for studying various corneal conditions and therapeutic applications.

