抄録
The goldfish retinal ganglion cells (RGCs) can survive and regenerate their axons after optic nerve injury. In a previous paper (Devadas et al., Neurosci. Res, 2001) we showed an increased activity of nitric oxide synthase (NOS) revealed by NADPH-diaphorase (ND) staining in the goldfish retina after optic nerve injury. The increase of ND activity was mainly localized in the ganglion cell layer (GCL). In the present study, to further elucidate molecular involvement of NOS in the optic nerve regeneration, we cloned a 490 bp cDNA fragment for goldfish neural NOS (nNOS) with a PCR teqhnique. Levels of nNOS mRNA and protein increased in the RGCs 5 days and peaked at 20-30 days, and then gradually returned to the control level by 60 days after injury. The period of 20-30 days after nerve injury corresponds to the axonal elongation stage in the goldfish optic nerve regeneration process. In retinal explant culture study, dibutyryl cyclic GMP (200-400 μM) and nitric oxide (NO) donor promoted neurite outgrowth, whereas ETPI, a nNOS inhibitor (10-40 μM) and soluble guanylate cyclase inhibitor (ODQ) dose-dependently suppressed it from adult fish RGCs. Furthermore, a specific PKG inhibitor, Rp-8-Br-PET cGMPs significantly inhibited the neurite outgrowth. The data all together indicate that NO-cGMP system is activated thereby leading to the promotion of optic nerve regeneration in the goldfish retina after injury. [J Physiol Sci. 2007;57 Suppl:S140]
