title: FK962 induces neurite outgrowth in cultured monkey trigeminal ganglion cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Senju Laboratory of Ocular Sciences, Senju Pharmaceutical Corporation Limited, Portland, OR, 97239, USA.|Department of Integrative Biosciences, Oregon Health & Science University, Portland, OR, 97239, USA.
authors: Emi
authors: E
authors: Nakajima
authors: Senju Laboratory of Ocular Sciences, Senju Pharmaceutical Corporation Limited, Portland, OR, 97239, USA.|Department of Integrative Biosciences, Oregon Health & Science University, Portland, OR, 97239, USA.
authors: Ryan D
authors: RD
authors: Walkup
authors: Department of Integrative Biosciences, Oregon Health & Science University, Portland, OR, 97239, USA.
authors: Thomas R
authors: TR
authors: Shearer
authors: Senju Laboratory of Ocular Sciences, Senju Pharmaceutical Corporation Limited, Portland, OR, 97239, USA. azumam@ohsu.edu.|Department of Integrative Biosciences, Oregon Health & Science University, Portland, OR, 97239, USA. azumam@ohsu.edu.
authors: Mitsuyoshi
authors: M
authors: Azuma
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D001549:Benzamides / Q000494:pharmacology*; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology / Q000294:innervation / Q000502:physiology; D008253:Macaca mulatta; D016501:Neurites / Q000187:drug effects*; D000071446:Neuronal Outgrowth / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D012677:Sensation / Q000187:drug effects; D012668:Trigeminal Ganglion / Q000166:cytology* / Q000187:drug effects
chemical_list: D001549:Benzamides; C507659:N-(1-acetylpiperidin-4-yl)-4-fluorobenzamide; D010880:Piperidines
keywords: FK962; GDNF; Neurite elongation; Non-human primate; Trigeminal nerve