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

作者：Wei Yanhong; Gong Junsong; Yoshida Takeshi; Eberhart Charles G; Xu Zhenhua; Kombairaju Ponvijay; S**** Michael B; Handa James T; Duh Elia J^*

来源：Free Radical Biology and Medicine, 2011, 51(1): 216-224.

DOI：10.1016/j.freeradbiomed.2011.04.026

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

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.

• 出版日期2011-7-1