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Sci Rep. 2018 Nov 16;8(1):16960. doi: 10.1038/s41598-018-35090-3.

Molecular basis of Mitomycin C enhanced corneal sensory nerve repair after debridement wounding.

Author information

1
Department of Anatomy and Cell Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA. mastepp@gwu.edu.
2
Department of Ophthalmology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA. mastepp@gwu.edu.
3
Department of Anatomy and Cell Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, 20037, USA.
4
Laboratory of Cancer Biology and Genetics, NCI, NIH, Bethesda, MD, 20892, USA.
5
Biodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
6
Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Abstract

The ocular surface is covered by stratified squamous corneal epithelial cells that are in cell:cell contact with the axonal membranes of a dense collection of sensory nerve fibers that act as sentinels to detect chemical and mechanical injuries which could lead to blindness. The sheerness of the cornea makes it susceptible to superficial abrasions and recurrent erosions which demand continuous regrowth of the axons throughout life. We showed previously that topical application of the antibiotic and anticancer drug Mitomycin C (MMC) enhances reinnervation of the corneal nerves and reduces recurrent erosions in mice via an unknown mechanism. Here we show using RNA-seq and confocal imaging that wounding the corneal epithelium by debridement upregulates proteases and protease inhibitors within the epithelium and leads to stromal nerve disruption. MMC attenuates these effects after debridement injury by increasing serpine1 gene and protein expression preserving L1CAM on axon surfaces of reinnervating sensory nerves. These data demonstrate at the molecular level that gene expression changes in the corneal epithelium and stroma modulate sensory axon integrity. By preserving the ability of axons to adhere to corneal epithelial cells, MMC enhances sensory nerve recovery after mechanical debridement injury.

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