April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
IL-17 and VEGF are Necessary for Efficient Corneal Nerve Regeneration
Author Affiliations & Notes
  • Zhijie Li
    Leukocyte Biology,
    Baylor College of Medicine, Houston, Texas
    Lab for Regenerative Medicine and Ophthalmology, Jinan University, Guangzhou, China
  • Debjani Gagen
    College of Optometry, University of Houston, Houston, Texas
  • Rolando Rumbaut
    Leukocyte Biology,
    Baylor College of Medicine, Houston, Texas
  • Alan R. Burns
    College of Optometry, University Eye Institute, Houston, Texas
  • Clifton W. Smith
    Baylor College of Medicine, Houston, Texas
  • Footnotes
    Commercial Relationships  Zhijie Li, None; Debjani Gagen, None; Rolando Rumbaut, None; Alan R. Burns, None; Clifton W. Smith, None
  • Footnotes
    Support  NIH EY018239, EY017120, HL079368, and NSF of China Grants 30672287, 30772387 and 81070703, and a Merit Review Grant from the Department of Veterans Affairs.
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2042. doi:
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      Zhijie Li, Debjani Gagen, Rolando Rumbaut, Alan R. Burns, Clifton W. Smith; IL-17 and VEGF are Necessary for Efficient Corneal Nerve Regeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2042.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : To explore the molecular mechanisms by which γΔ T cells promote corneal nerve regeneration after epithelial wounding.

Methods: : A 2 mm diameter central epithelial region was mechanically debrided in male C57BL/6J (WT), TCRdelta-/-, and WT mice with platelet depletion by anti-CD42b, neutrophil depletion by anti-Ly6G, IL-17 blocking by anti-IL-17, or VEGF blocking by anti-VEGF. Corneas from each group were harvested at different times after wounding, and whole mounted corneas were analyzed by deconvolution microscopy for γΔ T cell phenotypes in the epithelium, platelet accumulation in the limbus, neutrophil accumulation near the injured subbasal nerve plexus, and subbasal nerve density across corneas.

Results: : Abrasion induced accumulation of IL-17+ CCR6+ γΔ T cells, neutrophils and platelets in the cornea followed by full restoration of the epithelium and ~19% regeneration of sensory nerves within 96 hours. Mice deficient in γΔ T cells (TCRΔ-/-) or wildtype mice treated with anti-IL-17 had >50% reduction in neutrophil and platelet infiltration and >50% reduction in nerve regeneration. Depletion of either neutrophils or platelets in wild-type mice also resulted in >50% reductions in corneal nerve density. Infiltrating neutrophils and platelets stained positively for VEGF-A, tissue levels of VEGF-A peaked coincident with peak tissue levels of neutrophils and platelets, depletion of neutrophils prior to injury reduced tissue VEGF-A levels by >70%, and wildtype mice treated with anti-VEGF-A antibody exhibited >80% reduction in corneal nerve regeneration.

Conclusions: : The data presented here are consistent with the interpretation that CCR6+ IL-17+ γΔ T cells and IL-17 are necessary for early neutrophil and platelet-dependent delivery to the injured subbasal nerve plexus of VEGF-A, a trophic factor for neurite regeneration.

Keywords: wound healing • inflammation • regeneration 

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