FK962 induces neurite elongation in cultured monkey trigeminal ganglion cells

Abstract

LASIK refractive surgery is widely accepted for correcting myopia. Creation of the corneal flap in LASIK surgery can lead to dry eye due to amputation of corneal sensory nerves. Previous studies in the hippocampus showed that a substituted fluorobenzamide drug, FK962, caused release of neurotrophic peptides that stimulate and control nerve activity. Our studies in rabbits also showed that FK962 accelerated extension of neuronal processes and recovery of corneal sensitivity. The purposes of the present study were to 1) determine if FK962 induces spouting and elongation of neurites in cultured monkey trigeminal ganglion (TG) cells, and 2) investigate involvement of the neurotrophic peptide GDNF in FK‐induced neurite elongation. Dissociated, cultured TG cells, containing neuronal cells and Schwann cells, were cultured for 48 hours with or without FK962. Neuronal length and elongation were evaluated by staining with antibody for neurofilament specific to neurons. Culture with GDNF, or with antibody against GDNF, was used to determine the role of GDNF in neurite elongation. Our results showed that FK962, or GDNF alone, significantly induced neurite elongation. GDNF antibody significantly inhibited neurite elongation induced by FK962 or GDNF. Our data suggested that GDNF was a mediator of FK962‐induced neurite elongation. FK962 might be a candidate drug for treatment of complications after LASIK.Dr. Shearer receives consulting fees from, and Drs. Azuma and Nakajima are employees of, Senju Pharmaceutical Co. Ltd.