Corneal myofibroblasts inhibit regenerating nerves during wound healing

Scientific Reports
Kye-Im JeonKrystel R Huxlin

Abstract

Abnormal nerve regeneration often follows corneal injury, predisposing patients to pain, dry eye and vision loss. Yet, we lack a mechanistic understanding of this process. A key event in corneal wounds is the differentiation of keratocytes into fibroblasts and scar-forming myofibroblasts. Here, we show for the first time that regenerating nerves avoid corneal regions populated by myofibroblasts in vivo. Recreating this interaction in vitro, we find neurite outgrowth delayed when myofibroblasts but not fibroblasts, are co-cultured with sensory neurons. After neurites elongated sufficiently, contact inhibition was observed with myofibroblasts, but not fibroblasts. Reduced neurite outgrowth in vitro appeared mediated by transforming growth factor beta 1 (TGF-β1) secreted by myofibroblasts, which increased phosphorylation of collapsin response mediating protein 2 (CRMP2) in neurons. The significance of this mechanism was further tested by applying Mitomycin C after photorefractive keratectomy to decrease myofibroblast differentiation. This generated earlier repopulation of the ablation zone by intra-epithelial and sub-basal nerves. Our findings suggest that attaining proper, rapid corneal nerve regeneration after injury may require...Continue Reading

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Feb 16, 2019·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Thomas L A VolatierChe J Connon
Oct 1, 2019·Current Eye Research·Bhavani S Kowtharapu, Oliver Stachs
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Jan 20, 2022·Investigative Ophthalmology & Visual Science·Steven E WilsonRodrigo Carlos de Oliveira

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