The Role Of Peroxisome Proliferator-activated Receptor γ And Its Agonist, Pioglitazone,on A Rat Model Of Optic Nerve Crush

Objective To examined the change of PPARy expression in rat retina following optic nerve injury and investigated the effect of pioglitazone (Pio), a PPARy agonist on retinal ganglion cells (RGCs) neuroprotection using a rat optic nerve crush (ONC) model.Methods Adult SD rats were exposed to optic nerve injury by mechanic crushing on the left eye; the right eyes were untreated. Seventy-two rats were used for PPARy expression analysis and they were divided into8groups (n=9at each group):the control (received sham operation),1day (d),3d,5d,7d,14d,21d and28d after ONC. In each group,6rats were used for RT-PCR and Western blot analysis and3rats were used for immunohistochemistry detection. Ninety rats were enrolled in the pioglitazone (Pio) treatment experiment and they were randomly divided into5groups (n=18at each group):1) vehicle [0.1%dimethyl sulfoxide (DMSO)]-treated sham-operated group (sham group),2) vehicle-treated ONC group (vehicle group),3) Pio (10mg/kg Pio dissolved in DMSO)-treated ONC group (Pio group),4) PPARy antagonist GW9662(1.5mg/kg dissolved in DMSO)-treated ONC group (GW9662group), and5) Pio and GW9662-treated ONC group (Pio+GW9662group). Vehicle, Pio and GW9662were administered by intraperitoneal injection once a day after ONC or sham operation. In each group,6rats were used for RGCs retrograde labeling,6rats were used for TUNEL and immunofluorescence observation, and others were used for western blot.Results PPARy mRNA and protein levels were increased after ONC, and most of PPARy-immunoreactive cells colocalized with Muller cells. Pio treatment significantly enhanced the number of survival RGCs and inhibited RGCs apoptosis induced by ONC. However, when PPARy antagonist GW9662was used, these neuroprotective effects were abolished. In addition, pio attenuated Muller cell activation after ONC.Conclusions PPARy appears to protect RGCs from ONC possibly via the reduction of Muller glial activation. It provides evidence that activation of PPARy may be a potential alternative treatment for RGCs neuroprotection.