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Updated: May 21, 2026
An Epithelial Abrasion Model for Studying Corneal Wound Healing
Published on: December 29, 2021
Involvement of stem cell factor and c-kit in corneal wound healing in mice
Kazuhisa Miyamoto1, Takeshi Kobayashi, Yasuhito Hayashi
1Department of Ophthalmology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
Purpose:
To study the roles played by stem cell factor (SCF) and SCF receptor c-kit in wound healing of corneal epithelial cells.
Methods:
A 2 mm corneal epithelial wound was made in control (WBB6F1(+/+)), SCF (Sl/Sl(d))-, and c-kit (W/W(v)) mutant mice, and the speed of wound healing, 5-bromo-2'-deoxyuridine (BrdU) incorporation, and scanning electron microscopic (SEM) morphology of the corneas were examined. The incorporation of BrdU and the degree of cell attachment in cultured mouse corneal epithelial cells (MCECs) isolated from WBB6F1(+/+), Sl/Sl(d), and W/W(v) mice were examined. Cultured immortalized human corneal epithelial cells (HCECs) were examined by a cell attachment assay after their exposure to anti-SCF antibodies, tyrosine kinase inhibitor (genistein), and competitive Arg-Gly-Asp (RGD) peptide, as well as on cultures treated with extracellular matrix.
Results:
The speed of corneal wound healing was slower in Sl/Sl(d) and W/W(v) mice than in controls (p<0.01) and the speed of healing in Sl/Sl(d) mice recovered after topical application of SCF (8 ng/ml). No significant difference was found in the BrdU incorporation assay either in vivo or in vitro. Loosened epithelial cells were detected at wound margins in W/W(v) mice by SEM. The cell attachment rate was increased by 157% in cells from WBB6F1(+/+) and 252% in Sl/Sl(d) MCECs by recombinant mouse SCF; however, no significant difference was found in W/W(v) MCECs. Anti-SCF antibodies (Ab), genistein, and RGD peptide reduced the percentage of attached HCECs. Anti-SCF Ab inhibited the attachment of HCECs on fibronectin, laminin, or type IV collagen coated dishes.
Conclusions:
These findings indicate that the SCF/c-kit system may play a role in corneal wound healing through epithelial cell attachment.
Insights
The stem cell factor (SCF)/c-kit system is crucial for corneal wound healing. This system promotes epithelial cell attachment, which is vital for the healing process in the cornea.
Area of Science:
- Ophthalmology
- Cell Biology
- Regenerative Medicine
Background:
- Corneal wound healing is a complex process involving epithelial cell regeneration and migration.
- Stem cell factor (SCF) and its receptor c-kit are known to play roles in various cellular functions, including cell growth and differentiation.
Purpose of the Study:
- To investigate the role of the stem cell factor (SCF) and SCF receptor c-kit in the wound healing process of corneal epithelial cells.
Main Methods:
- Corneal epithelial wounds were created in control, SCF-deficient (Sl/Sl(d)), and c-kit-deficient (W/W(v)) mice.
- Wound healing speed, cell proliferation (BrdU incorporation), and corneal morphology (SEM) were assessed.
- In vitro studies involved examining cell attachment in cultured corneal epithelial cells from these mice and human corneal epithelial cells treated with SCF-related inhibitors.
Main Results:
- Corneal wound healing was significantly slower in SCF-deficient and c-kit-deficient mice compared to controls.
- Topical SCF application accelerated healing in SCF-deficient mice.
- Cell attachment assays revealed that SCF enhances epithelial cell attachment, while SCF antibodies and inhibitors reduce it, particularly on specific extracellular matrix components.
Conclusions:
- The SCF/c-kit signaling pathway plays a significant role in corneal wound healing.
- This role is primarily mediated through the regulation of corneal epithelial cell attachment.
