First Author | Li Z | Year | 2011 |
Journal | Am J Pathol | Volume | 178 |
Issue | 3 | Pages | 1106-16 |
PubMed ID | 21356362 | Mgi Jnum | J:169522 |
Mgi Id | MGI:4941243 | Doi | 10.1016/j.ajpath.2010.12.001 |
Citation | Li Z, et al. (2011) IL-17 and VEGF Are Necessary for Efficient Corneal Nerve Regeneration. Am J Pathol 178(3):1106-16 |
abstractText | The contribution of acute inflammation to sensory nerve regeneration was investigated in the murine cornea using a model of corneal abrasion that removes the stratified epithelium and subbasal nerve plexus. Abrasion induced accumulation of IL-17(+) CCR6(+) gammadelta T cells, neutrophils, and platelets in the cornea followed by full restoration of the epithelium and approximately 19% regeneration of sensory nerves within 96 hours. Mice deficient in gammadelta T cells (TCRdelta(-/-)) or wild-type mice treated systemically with anti-IL-17 had >50% reduction in leukocyte and platelet infiltration and >50% reduction in nerve regeneration. Strategies used to prevent neutrophil and platelet accumulation (eg, wild-type mice treated with anti-Ly6G or anti-GP1balpha antibody to deplete neutrophils or platelets) also resulted in >50% reductions in corneal nerve density. Infiltrating neutrophils and platelets stained positively for VEGF-A, tissue levels of VEGF-A peaked coincidentally with peak tissue levels of neutrophils and platelets, depletion of neutrophils before injury reduced tissue VEGF-A levels by >70%, and wild-type mice treated systemically with anti-VEGF-A antibody exhibited >80% reduction in corneal nerve regeneration. Given the known trophic effects of VEGF-A for neurite growth, the results in this report demonstrate a previously unrecognized beneficial role for the gammadelta T cell-dependent inflammatory cascade involving IL-17, neutrophils, platelets, and VEGF-A in corneal nerve regeneration. |