Abstract
It has been shown that peroxisome proliferators-activated receptor gamma (PPARγ) 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 PPARγ expression in rat retina following optic nerve injury and investigated the effect of pioglitazone (Pio), a PPARγ agonist, on retinal ganglion cells (RGCs) neuroprotection using a rat optic nerve crush (ONC) model. Our results showed that PPARγ mRNA and protein levels were increased after ONC, and most of PPARγ-immunoreactive cells colocalized with Müller cells. Pio treatment significantly enhanced the number of surviving RGCs and inhibited RGCs apoptosis induced by ONC. However, when PPARγ antagonist GW9662 was used, these neuroprotective effects were abolished. In addition, pio attenuated Müller cell activation after ONC. These results indicate that PPARγ appears to protect RGCs from ONC possibly via the reduction of Müller glial activation. It provides evidence that activation of PPARγ may be a potential alternative treatment for RGCs neuroprotection.
Highlights
Axon injury and loss of retinal ganglion cells (RGCs) are major pathological substrates for permanent visual disability in many ophthalmic diseases, such as glaucoma, optic nerve injury and ischemic optic neuropathy [1,2]
LTD) treatment experiment and they were randomly divided into 5 groups (n = 18 at each group): 1) sham group: rats were subjected to sham operation and administered vehicle [0.1% dimethyl sulfoxide (DMSO)], 2) vehicle group: rats were subjected to optic nerve crush (ONC) and administered vehicle, 3) Pio group: rats were subjected to ONC and administered Pio (10 mg/kg Pio dissolved in DMSO), 4) GW9662 group: rats were subjected to ONC and administered Peroxisome proliferator-activated receptor-c (PPARc) antagonist GW9662, and 5) Pio+GW9662 group: rats were subjected to ONC and administered Pio+GW9662
These PCR results were in line with the western blot analyses showing that the amount of PPARc protein was significantly higher after ONC (Fig. 1 B&C)
Summary
Axon injury and loss of retinal ganglion cells (RGCs) are major pathological substrates for permanent visual disability in many ophthalmic diseases, such as glaucoma, optic nerve injury and ischemic optic neuropathy [1,2]. Several common mechanisms have been hypothesized to underlie the processes of RGCs loss, including neurotrophic factor deprivation [3], glutamate-induced excitotoxicity [4], oxidative stress [5], reactive gliosis [6] and induction of pro-apoptotic pathways [7]. Based on these hypotheses, a variety of studies and strategies for providing neuroprotection to the injured retina have been proposed [8,9,10,11,12]. We observed the relationship between PPARc and retinal Muller cell activation
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