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Toru Nakazawa, Noriko Himori, Keiko Taguchi, Morin Ryu, Masayuki Yasuda, Kazuko Omodaka, Ahmed Shanab, Masayuki Yamamoto; Critical Role Of Nrf2 In The Oxidative Stress-induced Retinal Ganglion Cell Death. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3083.
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NF-E2 related factor2 (Nrf2) is a transcription factor that plays the pivot roles against the oxidative stress. However, the roles of Nrf2 in the visual systems remain unclear. Here, we investigate the functions of Nrf2 in the oxidative stress-induced retinal ganglion cell (RGC) death.
Sulforaphane (SFN, an Nrf2 activator, 1, 10, 100 nmol) was injected intravitreally and the expression of Nrf2 downstream transcriptions in the retina, including the antioxidant and phase II detoxifying enzymes (NQO1, HO-1, GSTA4, and TXNRD), were quantified by real-time PCR with Taqman probes. Retinal primary cultures of adult mice were prepared and cultured with Neurobasal A plus B28 supplement with (AO+) or without antioxidants (AO-). Surviving RGCs of wild-type (WT) and Nrf2 deficient (Nrf2KO) mice were compared by the cell count of the beta3 tubulin (a RGC marker) positive cells for 24h and 72h incubation.
Intravitreal administration of SFN significantly increased the expression of NQO1 (p=0.028), HO-1 (p=0.009) and TXNRD (p=0.009) in the retina. In vitro, the density of surviving RGCs of Nrf2KO mice were significantly less than that of WT mice (p=0.049). RGCs treated by intravitreal administration of SFN were significantly resistant to the oxidative stress than that of vehicle control (p=0.021).
Nrf2 had a potent neuroprotective effect against the oxidative stress in the retina through the induction of antioxidant and phase II detoxifying enzyme.
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