Open Access Highly Accessed Research article

Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage

Rajkumar Tulsawani1, Lorena S Kelly2, Nigar Fatma1, Bhavanaben Chhunchha1, Eri Kubo3, Anil Kumar4 and Dhirendra P Singh1*

Author affiliations

1 Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE, 68 198, USA

2 Department of Neurosurgery, University of Nebraska Medical Center, Omaha, NE, 68198, USA

3 Department of Ophthalmology, University of Fukui, Fukui, Japan

4 Department of Pharmacology and Toxicology, University of Missouri- Kansas City, Kansas City, MO, 64108, USA

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Citation and License

BMC Neuroscience 2010, 11:125  doi:10.1186/1471-2202-11-125

Published: 5 October 2010



The ability to respond to changes in the extra-intracellular environment is prerequisite for cell survival. Cellular responses to the environment include elevating defense systems, such as the antioxidant defense system. Hypoxia-evoked reactive oxygen species (ROS)-driven oxidative stress is an underlying mechanism of retinal ganglion cell (RGC) death that leads to blinding disorders. The protein peroxiredoxin 6 (PRDX6) plays a pleiotropic role in negatively regulating death signaling in response to stressors, and thereby stabilizes cellular homeostasis.


We have shown that RGCs exposed to hypoxia (1%) or hypoxia mimetic cobalt chloride display reduced expression of PRDX6 with higher ROS expression and activation of NF-κB. These cells undergo apoptosis, while cells with over-expression of PRDX6 demonstrate resistance against hypoxia-driven RGC death. The RGCs exposed to hypoxia either with 1% oxygen or cobalt chloride (0-400 μM), revealed ~30%-70% apoptotic cell death after 48 and 72 h of exposure. Western analysis and real-time PCR showed elevated expression of PRDX6 during hypoxia at 24 h, while PRDX6 protein and mRNA expression declined from 48 h onwards following hypoxia exposure. Concomitant with this, RGCs showed increased ROS expression and activation of NF-κB with IkB phosphorylation/degradation, as examined with H2DCF-DA and transactivation assays. These hypoxia-induced adverse reactions could be reversed by over-expression of PRDX6.


Because an abundance of PRDX6 in cells was able to attenuate hypoxia-induced RGC death, the protein could possibly be developed as a novel therapeutic agent acting to postpone RGC injury and delay the progression of glaucoma and other disorders caused by the increased-ROS-generated death signaling related to hypoxia.