Alpha-Crystallin Promotes Rat Axonal Regeneration Through Regulation of RhoA/Rock/Cofilin/MLC Signaling Pathways

Intravitreal injection of alpha-crystallin can promote axons from optic nerve regeneration after crushing in rats. We have previously demonstrated that alpha-crystallin can counteract the effect of myelin inhibitory factors and stimulate neurite growth. And a common crucial signaling event for myelin inhibitory factors is the activation of RhoA. To investigate whether alpha-crystallin counteracts the inhibitory effect of myelin inhibitory factors through regulation of RhoA/Rock signaling pathway, alpha-crystallin (10(-4) g/L) was injected into rat vitreous at the time the optic nerve crushed. The RhoA protein activity and the expression of RhoA and Rock were evaluated after 3 days of optic nerve axotomy. Rock downstream effectors, phosphorylated cofilin, and phosphorylated myosin light chain were detected when retinal neurons were cultured for 3 days. Axonal regeneration and neurites growth of cultured cells were observed also. Our results showed that alpha-crystallin decreased the RhoA protein activity and the phosphorylation of both cofilin and myosin light chain, and promoted the axonal growth. However, the expression of RhoA and Rock was not affected by alpha-crystallin. These findings indicated that alpha-crystallin could counteract the effect of myelin inhibitory factors through the regulation of RhoA/Rock signaling pathway.