Topical Mitomycin-C enhances subbasal nerve regeneration and reduces erosion frequency in the debridement wounded mouse cornea.
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.
Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, DC 20037, USA.
Sonali
S
Pal-Ghosh
Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, DC 20037, USA.
Ahdeah
A
Pajoohesh-Ganji
Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, DC 20037, USA.
Gauri
G
Tadvalkar
Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, DC 20037, USA; Physiology and Neuroscience Program, University of Maryland, College Park, MD 20740, USA.
Briana M
BM
Kyne
Massachusetts Eye and Ear Infirmary, Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Xiaoqing
X
Guo
Massachusetts Eye and Ear Infirmary, Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
James D
JD
Zieske
Department of Anatomy and Regenerative Biology, The George Washington University Medical School, Washington, DC 20037, USA; Department of Ophthalmology, The George Washington University Medical School, Washington, DC 20037, USA. Electronic address: mastepp@gwu.edu.
Mary Ann
MA
Stepp
D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D065306:Corneal Injuries / Q000188:drug therapy* / Q000473:pathology; D003646:Debridement; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects; D019573:Epithelium, Corneal / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D016685:Mitomycin / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D014945:Wound Healing / Q000502:physiology
D016685:Mitomycin
Cornea; Epithelium; Erosions; Mouse; Reinnervation; Subbasal nerves; Wound healing