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Topical Mitomycin-C enhances subbasal nerve regeneration and reduces erosion frequency in the debridement wounded
Sonali Pal-Ghosh1, Ahdeah Pajoohesh-Ganji1, Gauri Tadvalkar1
1Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, DC 20037, USA.
Abstract:
Corneal epithelial basement membrane dystrophies and superficial injuries caused by scratches can lead to recurrent corneal erosion syndrome (RCES). Patients and animals with reduced corneal sensory nerve innervation can also develop recurrent erosions. Multiple wild-type mouse strains will spontaneously develop recurrent corneal erosions after single 1.5 mm debridement wounds. Here we show that this wound is accompanied by an increase in corneal epithelial cell proliferation after wound closure but without a commensurate increase in corneal epithelial thickness. We investigated whether excess corneal epithelial cell proliferation contributes to erosion formation. We found that topical application of Mitomycin C (MMC), a drug used clinically to improve healing after glaucoma and refractive surgery, reduces erosion frequency, enhances subbasal axon density to levels seen in unwounded corneas, and prevents excess epithelial cell proliferation after debridement wounding. These results suggest that topically applied MMC, which successfully reduces corneal haze and scarring after PRK, may also function to enhance subbasal nerve regeneration and epithelial adhesion when used to treat RCES.
Insights
Recurrent corneal erosion syndrome (RCES) can be treated with Mitomycin C (MMC). This drug reduces erosion frequency, promotes nerve regeneration, and prevents excessive epithelial cell proliferation after corneal wounds.
Area of Science:
- Ophthalmology
- Regenerative Medicine
- Cell Biology
Background:
- Recurrent corneal erosion syndrome (RCES) and corneal injuries can result from basement membrane dystrophies or scratches.
- Reduced corneal sensory nerve innervation is linked to the development of recurrent erosions.
- Wild-type mice spontaneously develop recurrent corneal erosions after debridement wounds, characterized by increased epithelial cell proliferation without increased thickness.
Purpose of the Study:
- To investigate the role of excess corneal epithelial cell proliferation in the formation of recurrent corneal erosions.
- To evaluate the efficacy of topical Mitomycin C (MMC) in preventing and treating debridement-induced corneal erosions in mice.
Main Methods:
- Inducing debridement wounds in wild-type mouse strains.
- Administering topical Mitomycin C (MMC) post-wounding.
- Assessing corneal epithelial cell proliferation, thickness, subbasal axon density, and erosion frequency.
Main Results:
- Debridement wounds led to increased corneal epithelial cell proliferation post-closure, without a corresponding increase in corneal thickness.
- Topical MMC application significantly reduced the frequency of corneal erosions.
- MMC treatment enhanced subbasal axon density to levels observed in unwounded corneas and prevented excessive epithelial cell proliferation.
Conclusions:
- Excessive corneal epithelial cell proliferation may contribute to recurrent erosion formation.
- Topical Mitomycin C (MMC) demonstrates potential in treating recurrent corneal erosions by promoting nerve regeneration and improving epithelial adhesion.
- MMC's known efficacy in reducing corneal haze and scarring after PRK suggests a broader therapeutic role in corneal healing and regeneration.
