Sulforaphane decreases endothelial cell apoptosis in fuchs endothelial corneal dystrophy: a novel treatment.

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Fuchs endothelial corneal dystrophy (FECD ) is an oxidative stress disorder that leads to age-related and gradual loss of corneal endothelial cells resulting in corneal edema and loss of vision . To date , other than surgical intervention , there are no treatment options for patients with FECD . We have shown that in FECD , there is a deficiency in nuclear factor erythroid 2 -related factor 2 (Nrf 2 )-regulated antioxidant defense due to decreased Nrf 2 nuclear translocation and activation of antioxidant response element (ARE ). In this study , we used sulforaphane (SFN ) and D 3 T to investigate a strategy of targeting Nrf 2 -ARE in FECD .FECD and normal ex vivo corneas and human corneal endothelial cell lines were pretreated with SFN or D 3 T and exposed to oxidative stress with tert-Butyl hydroperoxide (tBHP ). Apoptosis was detected with TUNEL . Cellular localization of Nrf 2 and p 53 was assessed by immunohistochemistry . Effect of SFN was determined by using DCFDA assay , Western blot and real-time PCR .After pretreatment with SFN , oxidative stress was induced with tBHP . In ex vivo FECD specimens , SFN decreased CEC apoptosis by 55 % in unstressed group and by 43 % in tBHP-treated specimens . SFN enhanced nuclear translocation of Nrf 2 in FECD specimens and decreased p 53 staining under oxidative stress . Pretreatment with SFN enhanced cell viability by decreasing intracellular reactive oxygen species production . Upregulation of Nrf 2 levels led to increased synthesis of DJ-1 , heme oxygenase 1 , and nicotinamide adenine dinucleotide quinone oxidoreductase-1 . SFN significantly upregulated major ARE-dependent antioxidants and ameliorated oxidative stress-induced apoptosis in FECD .Our results suggest that targeting Nrf 2 -ARE pathway may arrest degenerative cell loss seen in FECD .