AUTHOR=Yao Fei , Zhang Xuan , Yao Xueyan , Ren Xiaohua , Xia Xiaobo , Jiang Jian , Ding Lexi 

TITLE=Peroxisome Proliferator-Activated Receptor α Activation Protects Retinal Ganglion Cells in Ischemia-Reperfusion Retinas

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.788663

DOI=10.3389/fmed.2021.788663

ISSN=2296-858X

ABSTRACT=<p><bold>Background and Objective:</bold> Retinal ischemia-reperfusion (IR) leads to massive loss of retinal ganglion cells (RGC) and characterizes several blind-causing ophthalmic diseases. However, the mechanism related to retinal IR is controversial, and a drug that could prevent the RGC loss caused by IR is still lacking. This study aimed to investigate the role of endogenous retinal peroxisome proliferator-activated receptor (PPAR)α and the therapeutic effect of its agonist, fenofibric acid (FA), in IR-related retinopathy.</p><p><bold>Materials and Methods:</bold> Fenofibric acid treatment was applied to the Sprague–Dawley rats with IR and retinal cell line 28 cells with oxygen-glucose deprivation (OGD) (an <italic>in vitro</italic> model of IR). Western blotting, real-time PCR, and immunofluorescence were used to examine the expression levels of PPARα, glial fibrillary acidic protein (GFAP), and cyclooxygenase-2 (COX2). Hematoxylin and eosin (HE) staining, propidium iodide (PI) staining, retrograde tracing, and flash visual-evoked potential (FVEP) were applied to assess RGC injury and visual function.</p><p><bold>Results:</bold> Retinal IR down-regulated PPARα expression <italic>in vitro</italic> and <italic>in vivo</italic>. Peroxisome proliferator-activated receptor α activation by FA promoted survival of RGCs, mitigated thinning of the ganglion cell complex, and decreased the latency of positive waves of FVEPs after IR injury. Further, FA treatment enhanced the expression of endogenous PPARα and suppressed the expression of GFAP and COX2 significantly.</p><p><bold>Conclusion:</bold> Peroxisome proliferator-activated receptor α activation by FA is protective against RGC loss in retinal IR condition, which may occur by restoring PPARα expression, inhibiting activation of glial cells, and suppressing retinal inflammation. All these findings indicate the translational potential of FA in treating IR-related retinopathy.</p>