Premium
Critical role of Nrf2 in oxidative stress‐induced retinal ganglion cell death
Author(s) -
Himori Noriko,
Yamamoto Kotaro,
Maruyama Kazuichi,
Ryu Morin,
Taguchi Keiko,
Yamamoto Masayuki,
Nakazawa Toru
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12325
Subject(s) - oxidative stress , retinal ganglion cell , keap1 , transcription factor , programmed cell death , biology , endogeny , retinal , retina , endocrinology , microbiology and biotechnology , apoptosis , medicine , chemistry , biochemistry , neuroscience , gene
NF ‐E2 related factor 2 (Nrf2) is a key transcription factor that plays a pivotal role in endogenous protection against oxidative stress. However, the role of Nrf2 in visual disorders remains unclear. It has been reported that oxidative stress is thought of as one of the causes of glaucoma. Here, we investigate whether the function of Nrf2 in oxidative stress‐induced retinal ganglion cell ( RGC ) death. This study used adult male Nrf2 deficient mice (Nrf2 KO ) and age‐ and sex‐matched wild‐type ( WT ) mice. We dissociated and purified N ‐4‐[4‐didecylaminostryryl]‐ N ‐methyl‐pyridinium iodide‐labeled RGC s with fluorescence‐activated cell sorting, and tried to detect the Nrf2 and Keap1 genes. In the absence of nerve crush ( NC ), the number of RGC s in Nrf2 KO mice was almost same as that in WT mice. 1‐(2‐cyano‐3‐, 12‐dioxooleana‐1, 9 (11)‐dien‐28‐oyl) imidazole ( CDDO ‐Im), an Nrf2 activator, prevented NC ‐induced loss of RGC s in WT mice. Seven days after NC , without treatment, the number of RGC s in Nrf2 KO mice was significantly lower than in WT mice. In addition, after CDDO ‐Im treatment, quantitative RT ‐ PCR showed increased expression of antioxidant and phase II detoxifying enzymes. These results suggest that up‐regulation of Nrf2 signaling after CDDO ‐Im treatment may be a novel therapeutic strategy for the protection of RGC s, especially in glaucoma.This study suggests that NF‐E2 related factor 2 (Nrf2), a transcription factor, plays a pivotal role in counteracting oxidative stress. Most importantly, a neuroprotective effect against oxidative stress‐induced retinal ganglion cell (RGC) death was achieved with the pharmacological Nrf2 activator CDDO‐Im. This suggests that pharmacological treatment to up‐regulate Nrf2 signaling may be a new therapeutic technique to protect RGCs.