Enhancement of Axonal Regeneration of Retinal Ganglion Cells in Adult Rats by Etomidate: Involvement of Protein Kinase C

Abstract

To investigate the effect of etomidate (ET) on axonal regeneration of retinal ganglion cells (RGCs) in adult rats. The optic nerve was transected intraorbitally at 1 mm from the optic disc, and an autologous peripheral nerve was transplanted onto the ocular ON stump in adult rats. Then the animals were treated with ET, Gö6976, ET combined with Gö6976, phorbol-12-myristate-13-acetate (PMA), or ET combined with PMA. Four weeks after grafting, the number of regenerating RGCs labeled retrogradely with neuronal retrograde tracer was counted in all animals, and the activity of membrane protein kinase C (mPKC) and cytoplasmic PKC (cPKC) was measured in ET-treated animals. The number of regenerating RGCs significantly increased when the dose of ET was increased from 2 mg/kg to 6 mg/kg, whereas the ratio of mPKC activity to cPKC activity significantly decreased in ET-treated animals. Gö6976, a potent conventional PKC inhibitor, also significantly increased the number of regenerating RGCs. However, the number of regenerating RGCs in animals treated with Gö6976 alone was significantly lower than in those treated with ET at 6 mg/kg. Combined treatment with ET at 6 mg/kg and Gö6976 did not increase the number of regenerating RGCs. In contrast, PMA, a potent PKC activator, partially abolished the positive effect of ET on the axonal regeneration of axotomized RGCs. These results suggest that ET promotes axonal regeneration of RGCs in adult rats, in part by inhibiting conventional PKC.