DIFFERENTIAL ACTIVATION OF P38 AND C-JUN N-TERMINAL KINASE IN THE VISUAL PATHWAY FOLLOWING OPTIC NERVE CRUSH

Purpose: p38 and c-jun N-terminal kinase (JNK) are two major stress-activated signaling pathways. In this study, we compared the activation of p38 and JNK in the retina, optic nerve, and superior colliculus after optic nerve crush (ONC) in adult mice. Methods: ONC was performed unilaterally in adult mice. The damage to the retinal ganglion cell (RGC) layer and superior colliculus (SC) was determined by Nissl and black gold II staining. The activation of p38 and JNK in the retina, optic nerve, and superior colliculus was examined by immunofluorescence staining. Results: Starting from 4 weeks after ONC, there were very few RGCs remaining in the RGC layer and fewer neurons (P < 0.05) in the contralateral SC compared to the control group. The volume of the contralateral SC was smaller (P < 0.01) than that of the control group. Phosphorylated JNK (p-JNK) was observed mainly on the proximal side of the optic nerve crush site as early as 1 hour after ONC. The expression of phosphorylated c-JUN was detected in the RGC layer starting 24 hours after ONC. The activation of p38 started 3 days post-ONC and was observed on both sides of the crush site. An increase of phosphorylated p38 (p-p38) was detected in the inner nuclear layer of the retina from 3 through 28 days following ONC. Two weeks after ONC, both p-JNK and p-p38 increased in the contralateral SC; however, the p38 activation was also observed in the ipsilateral SC. Conclusions: Optic nerve crush induces damage in both the RGC layer and the superior colliculus. p38 and JNK activation are differently modulated by optic nerve crush, and might play different roles in neuronal death in the retina and superior colliculus.