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Updated: Sep 30, 2025
An Epithelial Abrasion Model for Studying Corneal Wound Healing
Published on: December 29, 2021
Characterization of Recruited Mononuclear Phagocytes following Corneal Chemical Injury
Ricardo Lamy1, Marie Wolf1, Claudia Bispo2
1Department of Ophthalmology, University of California, San Francisco, CA 94158, USA.
Abstract:
Mononuclear phagocytes (MP) have central importance in innate immunity, inflammation, and fibrosis. Recruited MPs, such as macrophages, are plastic cells and can switch from an inflammatory to a restorative phenotype during the healing process. However, the role of the MPs in corneal wound healing is not completely understood. The purpose of this study is to characterize the kinetics of recruited MPs and evaluate the role of macrophage metalloelastase (MMP12) in the healing process, using an in vivo corneal chemical injury model. Unwounded and wounded corneas of wild-type (WT) and Mmp12 mice were collected at 1, 3, and 6 days after chemical injury and processed for flow cytometry analysis. Corneal MP phenotype significantly changed over time with recruited Ly6Chigh (proinflammatory) cells being most abundant at 1 day post-injury. Ly6Cint cells were highly expressed at 3 days post-injury and Ly6Cneg (patrolling) cells became the predominant cell type at 6 days post-injury. CD11c+ dendritic cells were abundant in corneas from Mmp12 mice at 6 days post-injury. These findings show the temporal phenotypic plasticity of recruited MPs and provide valuable insight into the role of the MPs in the corneal repair response, which may help guide the future development of MP-targeted therapies.
Insights
Mononuclear phagocytes (MPs) in the cornea shift phenotypes during healing. Macrophage metalloelastase (MMP12) influences MP kinetics and corneal repair.
Area of Science:
- Immunology
- Ophthalmology
- Cell Biology
Background:
- Mononuclear phagocytes (MPs), including macrophages, are crucial for innate immunity, inflammation, and fibrosis.
- MPs exhibit phenotypic plasticity, transitioning between inflammatory and restorative states during tissue repair.
- The specific role of MPs in corneal wound healing remains incompletely understood.
Purpose of the Study:
- To characterize the temporal dynamics (kinetics) of recruited MPs in the cornea following injury.
- To investigate the role of macrophage metalloelastase (MMP12) in the corneal wound healing process.
Main Methods:
- An in vivo mouse model of chemical corneal injury was utilized.
- Corneas from wild-type and Mmp12-deficient mice were analyzed at 1, 3, and 6 days post-injury using flow cytometry.
- Kinetics and phenotypic changes of corneal MPs were assessed over time.
Main Results:
- Corneal MP populations displayed significant temporal phenotypic changes post-injury.
- Recruited Ly6C®high (proinflammatory) MPs were most abundant at day 1.
- Ly6C®int cells peaked at day 3, and Ly6C®neg (patrolling) MPs predominated by day 6.
- Increased CD11c+ dendritic cells were observed in Mmp12-deficient corneas at day 6.
Conclusions:
- Recruited MPs demonstrate remarkable temporal phenotypic plasticity during corneal repair.
- MMP12 appears to influence the kinetics and composition of MP populations during corneal healing.
- Understanding MP dynamics offers potential targets for novel corneal repair therapies.
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