PACAP induces axonal elongation in cultured monkey trigeminal ganglion cells

Abstract

LASIK refractive surgery is widely accepted for correcting myopia. However, flap creation during LASIK surgery leads to complications including dry eye, caused by degeneration of sensory nerves. Our previous studies in rabbits showed that PACAP accelerated the extension of neuronal processes and recovered corneal sensitivity. The purposes of the present study were to 1) establish a cell culture system for monkey trigeminal nerve (TgN), whose fibers innervate cornea, and 2) determine if PACAP induces sprouting and elongation of axons. Expression of mRNA and cellular distribution for the PACAP receptor, PAC1, were determined by qPCR and immunostaining. Axonal length in cultured TgN ganglion cells was evaluated by staining with antibody for neurofilament. Our results showed that dissociated, cultured TgN ganglion cells contained neuronal and Schwann cells. The bioactive N‐terminal peptide PACAP27 significantly induced axonal elongation which was inhibited by the PAC1 antagonist PACAP 6–27. Downstream inhibitors of the PAC1 signaling pathway, AC and PKC, also inhibited axonal elongation. Together with positive PAC1 staining in neuronal cells, our data suggested involvement of PAC1 activation in axonal elongation. PACAP 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.