Capsaicin-induced corneal sensory denervation and healing impairment are reversed by NGF treatment

Alessandro Lambiase, Luigi Aloe, Flavio Mantelli, Marta Sacchetti, Eleonora Perrella, Patrizia Bianchi, Maria Luisa Rocco, Stefano Bonini

Research output: Contribution to journalArticle

Abstract

Purpose. We aimed to evaluate the nerve growth factor (NGF) pathway and its influence on corneal healing mechanisms in normal conditions and in an animal model of corneal denervation induced by capsaicin. Methods. Peripheral sensory damage was induced in rat pups by subcutaneous injection of capsaicin and the effects evaluated by hot-plate test, corneal nerve count, and tear secretion. Corneal damage was induced in capsaicin-treated and -untreated rats by epithelial scraping. Healing rate; NGF pathway (NGF, tyrosine kinase A [TrkA], p75); and the stem cell marker p63 were evaluated by RT-PCR, ELISA, Western blot, and immunohistochemistry. The effects of exogenous NGF administration as eye drop formulation were also tested. Results. Capsaicin treatment induced a significant reduction of peripheral sensitivity, corneal innervation, tear secretion, and corneal healing rate. The ocular effects of capsaicin treatment were associated with an NGF pathway alteration. NGF eye drop treatment aided corneal healing mechanisms through a significant increase in the NGF receptors TrkA and p75, and in the stem cell marker p63. Conclusions. In this study, we show that an alteration in the NGF pathway is responsible for a delay in corneal healing in an animal model of sensory denervation. Moreover, we show that NGF eye drop administration modulates corneal innervation, epithelial cell healing, and corneal stem cells. These findings may trigger further research on the role of the NGF pathway in limbal stem cell deficiency.

Original languageEnglish
Pages (from-to)8280-8287
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume53
Issue number13
DOIs
Publication statusPublished - Dec 2012

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Lambiase, A., Aloe, L., Mantelli, F., Sacchetti, M., Perrella, E., Bianchi, P., Rocco, M. L., & Bonini, S. (2012). Capsaicin-induced corneal sensory denervation and healing impairment are reversed by NGF treatment. Investigative Ophthalmology and Visual Science, 53(13), 8280-8287. https://doi.org/10.1167/iovs.12-10593