Prevention of Oxidative Stress-Induced Retinal Pigment Epithelial Cell Death by the PPARγ Agonist, 15-Deoxy-Delta 12, 14-Prostaglandin J2

Cellular oxidative stress plays an important role in retinal pigment epithelial (RPE) cell death during aging and the development of age-related macular degeneration. Early reports indicate that during phagocytosis of rod outer segments, there is an increase of RPE oxidative stress and an upregulation of PPAR gamma mRNA in these cells. These studies suggest that activation of PPAR gamma may modulate cellular oxidative stress. This paper presents a brief review of recent studies that investigate RPE oxidative stress under various experimental conditions. This is followed by a detailed review on those reports that examine the protective effect of the natural PPAR gamma ligand, 15d-PGJ(2), against RPE oxidative stress. This agent can upregulate glutathione and prevent oxidant-induced intracellular reactive oxygen species accumulation, mitochondrial depolarization, and apoptosis. The cytoprotective effect of this agent, however, is not shared by other PPAR gamma agonists. Nonetheless, this property of 15d-PGJ2 may be useful in future development of pharmacological tools against retinal diseases caused by oxidative stress. Copyright (C) 2008 Jason Y. Chang et al.