Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10738554 | Free Radical Biology and Medicine | 2011 | 9 Pages |
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 Nrf2â/â 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 Nrf2â/â mice. With regard to histopathologic damage, Nrf2â/â 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 Nrf2â/â mice. CDDO-Me treatment abrogated retinal capillary degeneration induced by I/R in wild-type but not Nrf2â/â 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.
Keywords
nuclear factor erythroid-2 related factor 2iOpMCP-1iNOSILMICAM-1COX-2HO-1Heme oxygenase-1Nrf2NQO1GCLCGCLMIL-6LPSNAD(P)H dehydrogenase, quinone 1CDDO-MeI/RROSinflammationischemia–reperfusioninterleukin-6Triterpenoidstumor necrosis factor-αApoptosisdihydroethidiuminducible nitric oxide synthaseCytokinesCyclooxygenase-2RetinaNF-E2-related factor 2internal limiting membraneTNF-αIntraocular pressurelipopolysaccharideglutamate-cysteine ligase, modifier subunitglutamate-cysteine ligase, catalytic subunitKnockout miceintercellular adhesion molecule-1DHEMonocyte chemotactic protein-1Reactive oxygen species
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Authors
Yanhong Wei, Junsong Gong, Takeshi Yoshida, Charles G. Eberhart, Zhenhua Xu, Ponvijay Kombairaju, Michael B. Sporn, James T. Handa, Elia J. Duh,