FK962 induces neurite outgrowth in cultured monkey trigeminal ganglion cells

Emi Nakajima, Ryan D. Walkup, Thomas (Tom) Shearer, Mitsuyoshi Azuma

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose: Corneal sensation, cell proliferation, and wound healing all depend on adequate corneal innervation. Disruption of corneal innervation can lead to dry eye and delayed wound healing. Our studies in rats and rabbits show that the substituted fluorobenzamide drug FK962 accelerates the extension of neuronal processes and recovery of corneal sensitivity. The purpose of the present study was 1) to determine whether FK962 induces sprouting and elongation of neurites in cultured monkey trigeminal ganglion cells, and 2) to investigate the involvement of the neurotrophic peptide GDNF in FK962-induced neurite elongation. Methods: Dissociated, cultured trigeminal ganglion cells, containing neuronal and Schwann cells were cultured for 48 h with or without FK962. Neuronal elongation was evaluated by immunostaining with a neurofilament-specific antibody. Culture with or without GDNF, or with antibody against GDNF, was used to determine the role of GDNF in FK962-induced neurite elongation. Results: FK962 or GDNF were found to significantly induce neurite elongation. The GDNF antibody significantly inhibited elongation induced by FK962. Conclusion: GDNF was found to be a mediator of FK962-induced neurite elongation in a relevant primate model. FK962 may be a candidate drug for treatment of neurotrophic disorders in the human cornea.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
DOIs
StateAccepted/In press - Oct 24 2016

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Trigeminal Ganglion
Glial Cell Line-Derived Neurotrophic Factor
Haplorhini
Neurites
Wound Healing
Antibodies
Neuronal Outgrowth
N-(1-acetylpiperidin-4-yl)-4-fluorobenzamide
Intermediate Filaments
Schwann Cells
Pharmaceutical Preparations
Cornea
Primates
Cell Proliferation
Rabbits
Peptides

Keywords

  • FK962
  • GDNF
  • Neurite elongation
  • Non-human primate
  • Trigeminal nerve

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

FK962 induces neurite outgrowth in cultured monkey trigeminal ganglion cells. / Nakajima, Emi; Walkup, Ryan D.; Shearer, Thomas (Tom); Azuma, Mitsuyoshi.

In: Graefe's Archive for Clinical and Experimental Ophthalmology, 24.10.2016, p. 1-6.

Research output: Contribution to journalArticle

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