April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
The neuroprotective role of Nrf2 in ischemia-reperfusion mouse model
Zhenhua Xu; Matthew Hartsock; Junsong Gong; Yanhong Wei; Shuang Wang; Elia J Duh
Author Affiliations & Notes
  • Zhenhua Xu
    Smith Building, Room 3001B, Johns Hopkins University, Baltimore, MD
  • Matthew Hartsock
    Smith Building, Room 3001B, Johns Hopkins University, Baltimore, MD
  • Junsong Gong
    Smith Building, Room 3001B, Johns Hopkins University, Baltimore, MD
  • Yanhong Wei
    Smith Building, Room 3001B, Johns Hopkins University, Baltimore, MD
  • Shuang Wang
    Smith Building, Room 3001B, Johns Hopkins University, Baltimore, MD
  • Elia J Duh
    Smith Building, Room 3001B, Johns Hopkins University, Baltimore, MD
  • Footnotes
    Commercial Relationships Zhenhua Xu, None; Matthew Hartsock, None; Junsong Gong, None; Yanhong Wei, None; Shuang Wang, None; Elia Duh, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1906. doi:
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      Zhenhua Xu, Matthew Hartsock, Junsong Gong, Yanhong Wei, Shuang Wang, Elia J Duh; The neuroprotective role of Nrf2 in ischemia-reperfusion mouse model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1906.

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Abstract

Purpose: Nrf2 is known to play a protective role in regulating oxidative stress and inflammation. Our group previously found that Nrf2 plays a cytoprotective role in murine models of retinal ischemia-reperfusion and diabetic retinopathy. The objective of this study was to explore the potential neuroprotective role of Nrf2 in the mouse ischemia-reperfusion model.

Methods: Retinal ischemia-reperfusion model was performed by elevating intraocular pressure to 90mmHg for 90 min. NeuN immunostaining of retina flat-mount and H/E staining of paraffin-embedded sections were used to determine cell loss in the ganglion cell layer. RGC-5 cells, a retinal neuronal cell line, were treated with different doses of Tert-Butyl hydroperoxide (TBH), and the level of reactive oxygen species (ROS) was measured by DCF assay. Keap1 siRNA was used to up-regulate Nrf2 activity in RGC-5 cells. The synthetic triterpenoid CDDO-Im (2-Cyano-3,12-dioxooleana-1,9-dien-28-imidazolide) was used to activate Nrf2 expression in RGC-5 cells.

Results: In the retinal ischemia-reperfusion mouse model, cell loss in ganglion cell layer was much more severe in Nrf2 knockout mice than in wild-type mice at 2 and 7 days after I/R. There was significantly more apoptosis in Nrf2 KO retinas compared to wild-type. Treatment with TBH increased ROS level in RGC-5 cells. siRNA-mediated knockdown of the Nrf2 inhibitor Keap1 exacerbated this TBH-induced ROS increase. Pharmacologic activation of Nrf2 using the triterpenoid CDDO-Im inhibited TBH-induced ROS increase in a dose-dependent fashion.

Conclusions: These results indicate that Nrf2 exhibits a neuronal protective function in the retinal ischemia-reperfusion model and suggest that pharmacologic activation of Nrf2 could be a therapeutic strategy.

Keywords: 572 ischemia • 615 neuroprotection  
© 2014, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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