PLK2 protects retinal ganglion cells from oxidative stress by potentiating Nrf2 signaling via GSK-3β.

Oxidative stress of retinal ganglion cells (RGCs) has been established as a main contributor to retinal degeneration in the pathogenesis of glaucoma. Polo-like kinase 2 (PLK2) has recently been reported to be a potent antioxidant protein that enhances cell survival in response to oxidative stress. To date, the involvement of PLK2 in RGC-associated oxidative stress is undermined. In the present work, we evaluated whether PLK2 regulates oxidative stress evoked by hydrogen peroxide (H O ) in RGCs. PLK2 expression was induced by H O stimulation in RGCs. Upregulation of PLK2 had a profoundly cytoprotective effect on H O -stimulated RGCs by attenuating cellular apoptosis and reactive oxygen species (ROS) level. Further data revealed that upregulation of PLK2 strikingly enhanced the activation of Nrf2 signaling. Moreover, PLK2 overexpression promoted glycogen synthase kinase (GSK)-3β phosphorylation, whereas PLK2 knockdown reduced the levels of GSK-3β phosphorylation. Notably, GSK-3β inhibition using a chemical inhibitor markedly abrogated the suppressive effects of PLK2 knockdown on Nrf2 activation. Repression of Nrf2 blocked the PLK2 overexpression-induced protective effects in H O -stimulated RGCs. Overall, this study elucidates that upregulation of PLK2 protects RGCs against H O -induced oxidative stress injury by upregulating Nrf2 activation via modulation of GSK-3β phosphorylation. These findings underline the pivotal role of PLK2 in mediating oxidative stress-evoked retinal degeneration in the pathogenesis of glaucoma.