The role of peroxisome proliferator-activated receptor and effects of its agonist, pioglitazone, on a rat model of optic nerve crush: PPARγ in retinal neuroprotection

PLoS One. 2013 Jul 18;8(7):e68935. doi: 10.1371/journal.pone.0068935. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Anilides / pharmacology
  • Animals
  • Blotting, Western
  • Fluorescent Antibody Technique
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / physiology
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Neuroprotective Agents / pharmacology*
  • Optic Nerve Injuries / drug therapy*
  • Optic Nerve Injuries / metabolism
  • PPAR gamma / agonists
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / metabolism*
  • Pioglitazone
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Retinal Ganglion Cells / drug effects*
  • Thiazolidinediones / pharmacology*

Substances

  • 2-chloro-5-nitrobenzanilide
  • Anilides
  • Neuroprotective Agents
  • PPAR gamma
  • Thiazolidinediones
  • Pioglitazone

Grants and funding

This work was supported by a grant from the science and technology project of Nantong, China (No. BK2012070), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and the National Natural Science Foundation of China (No:81200680). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.