Nrf2 has a protective role against neuronal and capillary degeneration in retinal ischemia-reperfusion injury

Yanhong Wei, Junsong Gong, Takeshi Yoshida, Charles G. Eberhart, Zhenhua Xu, Ponvijay Kombairaju, Michael B. Sporn, James T. Handa, Elia J. Duh

Research output: Contribution to journalArticle

Abstract

Retinal ischemia-reperfusion (I/R) involves an extensive increase in reactive oxygen species as well as proinflammatory changes that result in significant histopathologic damage, including neuronal and vascular degeneration. Nrf2 has a well-known cytoprotective role in many tissues, but its protective function in the retina is unclear. We investigated the possible role of Nrf2 as a protective mechanism in retinal ischemia-reperfusion injury using Nrf2 -/- mice. I/R resulted in an increase in retinal levels of superoxide and proinflammatory mediators, as well as leukocyte infiltration of the retina and vitreous, in Nrf2 +/+ mice. These effects were greatly accentuated in Nrf2 -/- mice. With regard to histopathologic damage, Nrf2 -/- mice exhibited loss of cells in the ganglion cell layer and markedly accentuated retinal capillary degeneration, as compared to wild-type. Treatment with the Nrf2 activator CDDO-Me increased antioxidant gene expression and normalized I/R-induced superoxide in the retina in wild-type but not Nrf2 -/- mice. CDDO-Me treatment abrogated retinal capillary degeneration induced by I/R in wild-type but not Nrf2 -/- mice. These studies indicate that Nrf2 is an important cytoprotective mechanism in the retina in response to ischemia-reperfusion injury and suggest that pharmacologic induction of Nrf2 could be a new therapeutic strategy for retinal ischemia-reperfusion and other retinal diseases.

Original languageEnglish (US)
Pages (from-to)216-224
Number of pages9
JournalFree Radical Biology and Medicine
Volume51
Issue number1
DOIs
StatePublished - Jul 1 2011

Keywords

  • Apoptosis
  • Capillary degeneration
  • Cytokines
  • Inflammation
  • Ischemia-reperfusion
  • Knockout mice
  • Nuclear factor erythroid-2 related factor 2
  • Reactive oxygen species
  • Retina
  • Triterpenoids

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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