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MINGLI QU, QINGJUN ZHOU; Impaired activation of Nrf2-ARE signaling pathway: a possible mechanism for Keratoconus. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1930.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the activation defect of NF-E2-related factor 2-antioxidant response element (Nrf2-ARE) signaling in Keratoconus corneal stromal cells and to investigate the underlying mechanisms involved in the pathogenesis of Keratoconus.
Corneal stromal cells were isolated from Keratoconus and normal cornea by using Dispase and collagenase digestion. Reactive oxygen species (ROS) production was measured by fluorescence substrate DCHF-DA incubation. Nuclear Nrf2 level and the expression of Nrf2-ARE downstream antioxidant genes were analyzed by western blot and real time quantitative-polymerase chain reaction (RT-qPCR). The expression and activity of matrix degenerating enzymes, including urokinase-type plasminogen activator (uPA)-uPA receptor (uPAR) system and matrix metalloproteinase-2 (MMP-2) were assessed by western blot and gelatin zymography.
The Keratoconus corneal stromal cells showed higher nuclear Nrf2 level than that of normal corneal stromal cells, while the expression levels of Nrf2-ARE downstream antioxidant genes were lower than normal cornea. Moreover, Keratoconus corneal stromal cells assumed increased production of ROS, the expressions and activities of matrix degenerating enzymes were higher when compared with normal cornea.
Keratoconus corneal stromal cells showed significant activation defect of Nrf2-ARE signaling pathway and up-regulated expression of matrix degenerating enzymes, which may be involved in the pathogenesis of Keratoconus.
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