Injury-specific pathways shape corneal nerve regeneration dynamics

Abstract The cornea, a transparent tissue critical for clear vision, is uniquely characterized by a dense network of peripheral sensory nerves. This innervation not only enables sensation but also provides vital trophic support, ensuring corneal health and integrity. Damage or loss of these peripher...

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Main Authors: Léna Meneux, Sarah Pernot, Nadège Feret, Melissa Girard, Alicia Caballero Megido, Marilou Decoudu, Naima Nhiri, Elea Miessen, Eric Jacquet, Vincent Daien, Frederic Michon
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-10434-y
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author Léna Meneux
Sarah Pernot
Nadège Feret
Melissa Girard
Alicia Caballero Megido
Marilou Decoudu
Naima Nhiri
Elea Miessen
Eric Jacquet
Vincent Daien
Frederic Michon
author_facet Léna Meneux
Sarah Pernot
Nadège Feret
Melissa Girard
Alicia Caballero Megido
Marilou Decoudu
Naima Nhiri
Elea Miessen
Eric Jacquet
Vincent Daien
Frederic Michon
author_sort Léna Meneux
collection DOAJ
description Abstract The cornea, a transparent tissue critical for clear vision, is uniquely characterized by a dense network of peripheral sensory nerves. This innervation not only enables sensation but also provides vital trophic support, ensuring corneal health and integrity. Damage or loss of these peripheral nerves leads to neurotrophic keratitis (NK), a debilitating condition that disrupts corneal healing and function, ultimately threatening vision. Remarkably similar to other peripheral neuropathies, NK arises from various injuries, diseases, or surgical interventions, yet its underlying regenerative mechanisms remain poorly understood, limiting effective treatment options. In this study, we investigated how corneal nerves regenerate following two different types of clinically relevant injuries—axotomy (mimicking nerve damage during corneal transplantation) and epithelial abrasion (resembling superficial corneal surgery). We found that the type of injury distinctly influences both the structural and functional recovery of corneal nerves. Axotomy resulted in delayed nerve regeneration, significant disruption of epithelial cell homeostasis, and increased risk of severe corneal damage. Conversely, epithelial abrasion induced rapid but structurally abnormal nerve recovery. Furthermore, we identified specific molecular pathways activated differently depending on injury type. Our findings highlight the complexity of peripheral nerve regeneration, underscoring the necessity for targeted therapeutic strategies tailored to individual injury scenarios. By illuminating the variability in nerve recovery, our study provides valuable insights applicable not only to NK but potentially to a broader spectrum of peripheral neuropathies, paving the way for novel therapeutic interventions.
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spelling doaj-art-4d246bfd5d2f497b842e6ddd06f0aa5c2025-08-20T03:45:59ZengNature PortfolioScientific Reports2045-23222025-07-0115111810.1038/s41598-025-10434-yInjury-specific pathways shape corneal nerve regeneration dynamicsLéna Meneux0Sarah Pernot1Nadège Feret2Melissa Girard3Alicia Caballero Megido4Marilou Decoudu5Naima Nhiri6Elea Miessen7Eric Jacquet8Vincent Daien9Frederic Michon10Institute for Neurosciences of Montpellier, INSERM, Univ MontpellierInstitute for Neurosciences of Montpellier, INSERM, Univ MontpellierInstitute for Neurosciences of Montpellier, INSERM, Univ MontpellierInstitute for Neurosciences of Montpellier, INSERM, Univ MontpellierInstitute for Neurosciences of Montpellier, INSERM, Univ MontpellierInstitute for Neurosciences of Montpellier, INSERM, Univ MontpellierInstitut de Chimie des Substances Naturelles, CNRS UPR2301, Paris-Saclay UniversityInstitute for Neurosciences of Montpellier, INSERM, Univ MontpellierInstitut de Chimie des Substances Naturelles, CNRS UPR2301, Paris-Saclay UniversityInstitute for Neurosciences of Montpellier, INSERM, Univ MontpellierInstitute for Neurosciences of Montpellier, INSERM, Univ MontpellierAbstract The cornea, a transparent tissue critical for clear vision, is uniquely characterized by a dense network of peripheral sensory nerves. This innervation not only enables sensation but also provides vital trophic support, ensuring corneal health and integrity. Damage or loss of these peripheral nerves leads to neurotrophic keratitis (NK), a debilitating condition that disrupts corneal healing and function, ultimately threatening vision. Remarkably similar to other peripheral neuropathies, NK arises from various injuries, diseases, or surgical interventions, yet its underlying regenerative mechanisms remain poorly understood, limiting effective treatment options. In this study, we investigated how corneal nerves regenerate following two different types of clinically relevant injuries—axotomy (mimicking nerve damage during corneal transplantation) and epithelial abrasion (resembling superficial corneal surgery). We found that the type of injury distinctly influences both the structural and functional recovery of corneal nerves. Axotomy resulted in delayed nerve regeneration, significant disruption of epithelial cell homeostasis, and increased risk of severe corneal damage. Conversely, epithelial abrasion induced rapid but structurally abnormal nerve recovery. Furthermore, we identified specific molecular pathways activated differently depending on injury type. Our findings highlight the complexity of peripheral nerve regeneration, underscoring the necessity for targeted therapeutic strategies tailored to individual injury scenarios. By illuminating the variability in nerve recovery, our study provides valuable insights applicable not only to NK but potentially to a broader spectrum of peripheral neuropathies, paving the way for novel therapeutic interventions.https://doi.org/10.1038/s41598-025-10434-yCorneaInnervationDevelopmentRegeneration
spellingShingle Léna Meneux
Sarah Pernot
Nadège Feret
Melissa Girard
Alicia Caballero Megido
Marilou Decoudu
Naima Nhiri
Elea Miessen
Eric Jacquet
Vincent Daien
Frederic Michon
Injury-specific pathways shape corneal nerve regeneration dynamics
Scientific Reports
Cornea
Innervation
Development
Regeneration
title Injury-specific pathways shape corneal nerve regeneration dynamics
title_full Injury-specific pathways shape corneal nerve regeneration dynamics
title_fullStr Injury-specific pathways shape corneal nerve regeneration dynamics
title_full_unstemmed Injury-specific pathways shape corneal nerve regeneration dynamics
title_short Injury-specific pathways shape corneal nerve regeneration dynamics
title_sort injury specific pathways shape corneal nerve regeneration dynamics
topic Cornea
Innervation
Development
Regeneration
url https://doi.org/10.1038/s41598-025-10434-y
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