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Updated: Oct 4, 2025
An Epithelial Abrasion Model for Studying Corneal Wound Healing
Published on: December 29, 2021
dsRNA Induced IFNβ-MMP13 Axis Drives Corneal Wound Healing
Xihong Lan1, Wang Zhang1, Jin Zhu1
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Purpose:
Cornea, the outermost transparent layer of the eye, is the first line of defense against external threats. Following injury, the wound healing response is crucial to corneal repair and regeneration, yet its underlying mechanism is poorly understood. Our study was designed to investigate the role of dsRNA and its regulatory network in corneal wound healing.
Methods:
A corneal wound healing model was established via the surgical removal of half of the corneal surface and adjoining limbus. RNase III was then used to clarify the role of dsRNA in corneal wound closure and RNA-seq was performed to investigate the mechanism of dsRNA in the healing process. Related gene expression was assessed using immunofluorescence staining, qPCR, and Western blot. Flow cytometry and scratch assay were used to analyze the proliferation and migration of limbal stem/progenitor cells (LSCs) in vitro and functional analysis of the target genes was completed using the corneal wound healing model.
Results:
Corneal wound healing was delayed and impaired when the dsRNAs were removed or damaged following RNase III digestion. The dsRNAs released following corneal damage activate type I interferon (IFN-I) signaling, primarily IFNβ, via the corneal epithelium and neutralizing IFNβ or blocking IFN-I signaling delays corneal wound closure. Moreover, our data identified MMP13 as a downstream effector of IFNβ where its expression promotes LSC proliferation and enhances corneal epithelial reconstruction in vivo.
Conclusions:
The dsRNA induced IFNβ-MMP13 axis plays a key role in corneal wound healing.
Insights
Double-stranded RNA (dsRNA) released after corneal injury activates type I interferon (IFN-I) signaling, promoting healing. This dsRNA-induced IFN-I signaling pathway, involving IFNβ and MMP13, is crucial for corneal repair and limbal stem cell regeneration.
Area of Science:
- Ophthalmology
- Immunology
- Regenerative Medicine
Background:
- The cornea's wound healing process is vital for vision but not fully understood.
- Double-stranded RNA (dsRNA) is implicated in cellular responses to damage.
Purpose of the Study:
- To investigate the role of dsRNA and its regulatory network in corneal wound healing.
- To elucidate the mechanism by which dsRNA influences corneal repair.
Main Methods:
- Established a corneal wound healing model and used RNase III to assess dsRNA's role.
- Employed RNA-sequencing, immunofluorescence, qPCR, and Western blot to analyze gene expression.
- Utilized flow cytometry and scratch assays to evaluate limbal stem/progenitor cell (LSC) behavior.
Main Results:
- Corneal wound healing was impaired upon dsRNA removal or degradation.
- dsRNA activates type I interferon (IFN-I) signaling, primarily IFNβ, in corneal epithelium.
- IFNβ signaling promotes LSC proliferation and corneal epithelial reconstruction, with MMP13 identified as a key downstream effector.
Conclusions:
- The dsRNA-induced IFNβ-MMP13 axis is essential for effective corneal wound healing.
- Targeting this pathway could offer therapeutic strategies for corneal repair.
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