Y-39983 downregulates RhoA/Rho-associated kinase expression during its promotion of axonal regeneration

Abstract

Y-39983, a selective Rho-associated kinase (ROCK) inhibitor, promotes axonal regeneration of damaged retinal ganglion cells (RGCs). The present study investigated the effects of Y-39983 on RhoA/ROCK expression during promotion of axonal regeneration using a rat optic nerve crush (ONC) model. Herein, we demonstrated that Y-39983 significantly enhanced the survival and axonal regeneration of RGCs after ONC. Using a pull-down assay and affinity precipitation to examine the activity of RhoA, we detected the decreased expression of active-RhoA after using Y-39983. The expression of ROCK1 and ROCK2 was significantly decreased as demonstrated by RT-PCR, immunohistochemistry and western blot analysis. The downregulation of active-RhoA, ROCK1 and ROCK2 expression by Y-39983 coincided with the appearance of larger numbers of regenerating axons. In conclusion, Y-39983 downregulated the expression of active-RhoA, ROCK1 and ROCK2 during its promotion of axonal regeneration.