June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Nerve Growth Factor Mediates Corneal Lymphangiogenesis
Author Affiliations & Notes
  • Tatiana Ecoiffier
    Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, CA
  • Pedram Hamrah
    Schepens Eye Research Institute, Massachusetts Eye & Ear, Department of Ophthalmology, Harvard Medical School, Boston, CA
  • Sammy Grimaldo
    Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, CA
  • Gyeong Jin Kang
    Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, CA
  • Roberto Sessa
    Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, CA
  • Tan Ngoc Truong
    Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, CA
  • Deshea L Harris
    Schepens Eye Research Institute, Massachusetts Eye & Ear, Department of Ophthalmology, Harvard Medical School, Boston, CA
  • Ulrich von Andrian
    Immune Disease Institute, Program in Cellular and Molecular Medicine at Children’s Hospital Boston, Harvard Medical School, Boston, CA
  • Lu Chen
    Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, CA
  • Lixin Zheng
    Schepens Eye Research Institute, Massachusetts Eye & Ear, Department of Ophthalmology, Harvard Medical School, Boston, CA
  • Footnotes
    Commercial Relationships Tatiana Ecoiffier, None; Pedram Hamrah, None; Sammy Grimaldo, None; Gyeong Jin Kang, None; Roberto Sessa, None; Tan Truong, None; Deshea Harris, None; Ulrich von Andrian, None; Lu Chen, None; Lixin Zheng, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4504. doi:
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      Tatiana Ecoiffier, Pedram Hamrah, Sammy Grimaldo, Gyeong Jin Kang, Roberto Sessa, Tan Ngoc Truong, Deshea L Harris, Ulrich von Andrian, Lu Chen, Lixin Zheng; Nerve Growth Factor Mediates Corneal Lymphangiogenesis. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4504.

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

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Abstract

Purpose: Lymphangiogenesis (LG), the growth of new lymphatic vessels, is a critical process involved in many pathological conditions, including cancer metastasis, tissue inflammation and graft rejection. This study was designed to investigate the critical role of nerve growth factor (NGF) in mediating corneal LG by using a repertoire of in vivo, in vitro and in real-time models and methods.

Methods: A variety of in vivo corneal LG and nerve injury models (pellet implantation, cautery, trephination, axotomy and transplantation), ex vivo immunofluoresent microscopic assays, intravital imaging technology, and in vitro lymphatic endothelial cell (LEC) culture systems were used to investigate NGF expressional changes during corneal LG, the role of NGF in inducing corneal LG in vivo and in real-time, and the role of NGF in mediating LEC functions in vitro.

Results: NGF was significantly increased during corneal LG and nerve damage and it mediated LG in both dose- and time-dependent manners. NGF also directly mediated LEC functions in vitro. Anti-NGF treatment suppressed NGF-induced LG in micropocket assay. However, it exacerbated LG after nerve injury. Accordingly, NGF administration inhibited LG during concurrent nerve injury.

Conclusions: Our study suggests that NGF has a dual function by maintaining nerve survival at a critical level, while inducing LG at higher concentrations. This study not only offers a direct link between NGF and LG, but also reveals a critical balance that is regulated by NGF between the lymphatic and nerve supplies within a tissue, which necessitates consideration in therapeutic approaches.

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