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Mamiko Noda, Yayoi Kishimoto, Chiho Yabuta, Thomas R. Shearer, Mitsuyoshi Azuma; Role of GDNF in FK962-induced Neurite Elongation of Cultured Rat Trigeminal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1799.
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© ARVO (1962-2015); The Authors (2016-present)
Denervation of the cornea can lead to dry eye, which may occur after in situ keratomileusis (LASIK) for correcting myopia. Our previous study showed that N-(1-acetylpiperidin-4-yl)-4-fluorobenzamide (FK962) induced elongation of axon from transected nerve termini and accelerated recovery of corneal sensitivity in a rabbit model of flap surgery. We also reported that FK962 induced neurite elongation in cultured trigeminal ganglion (TG) cells from rabbits and rats. Although an analog of FK962 caused production of glial cell line-derived neurotrophic factor (GDNF) in cultured astrocytes, the molecular mechanism for the action of FK962 in neurite elongation is not yet well defined. Thus, the purpose of the present experiment was to investigate the mechanism of FK962-induced neurite elongation.
Trigeminal ganglion cells (neuronal + Schwann cells) were cultured with or without FK962. Cells were fixed, labeled with antibody for neurofilaments, and observed with a fluorescence microscope. Nerve growth factor (NGF) and GDNF were used as positive controls for neurite elongation, and antibody neutralization was used to determine the mechanism for FK962-induced neurite elongation. Expression of mRNAs for GDNF and the GFRα1 subunit of the GDNF receptor complex were measured by qPCR.
FK962 induced sprouting and elongation of neurites in TG neurons. GDNF treatment also induced neurite elongation. GDNF antibody inhibited neurite elongation induced by GDNF and FK962. NGF also induced neurite elongation, which was inhibited by NGF antibody, but NGF antibody did not inhibit FK962-induced neurite elongation. Levels of mRNAs for GDNF and GFRα1 were high in TG cells compare to brain.
Our data suggested that FK962 stimulated induction of GDNF, which may be a part of the mechanism for FK-induced neurite elongation in rat TG neurons.
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