The Role of Peroxisome Proliferator-Activated Receptor and Effects of Its Agonist, Pioglitazone, on a Rat Model of Optic Nerve Crush: PPAR gamma in Retinal Neuroprotection

It has been shown that peroxisome proliferators-activated receptor gamma (PPAR gamma) is beneficial for central nervous system injury. However its role on optic nerve injury remains unknown. In the present study, we examined the change of PPAR gamma expression in rat retina following optic nerve injury and investigated the effect of pioglitazone (Pio), a PPAR gamma agonist, on retinal ganglion cells (RGCs) neuroprotection using a rat optic nerve crush (ONC) model. Our results showed that PPAR gamma mRNA and protein levels were increased after ONC, and most of PPAR gamma-immunoreactive cells colocalized with Muller cells. Pio treatment significantly enhanced the number of surviving RGCs and inhibited RGCs apoptosis induced by ONC. However, when PPAR gamma antagonist GW9662 was used, these neuroprotective effects were abolished. In addition, pio attenuated Muller cell activation after ONC. These results indicate that PPAR gamma appears to protect RGCs from ONC possibly via the reduction of Muller glial activation. It provides evidence that activation of PPAR gamma may be a potential alternative treatment for RGCs neuroprotection.