Dimethyl Fumarate Promotes the Survival of Retinal Ganglion Cells after Optic Nerve Injury,Possibly through the Nrf2/HO-1 Pathway |
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Authors: | Sotaro Mori Takuji Kurimoto Hidetaka Maeda Makoto Nakamura |
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Affiliation: | 1.Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan; (S.M.); (M.N.);2.Maeda Eye Clinic, 1-1-1 Uchihonmachi, Chuo-ku, Osaka 540-0012, Japan; |
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Abstract: | This study aimed to verify whether dimethyl fumarate (DMF) promotes the survival of retinal ganglion cells (RGCs) after optic nerve crush (ONC) accompanied by activation of the NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. We examined changes in the densities of tubulin β3 (TUBB3)-positive RGCs and the amplitudes of the positive scotopic threshold response (pSTR), reflecting the functional activity of RGCs, recorded on an electroretinogram, with daily administration of DMF, on day 7 after ONC. Furthermore, immunohistochemical and immunoblotting analyses were performed to study the activation of the Nrf2/HO-1 pathway using retinas treated with daily administration of DMF. Daily administration of DMF increasedthe density of TUBB3-positive RGCs in a dose-dependent fashion and significantly increased the amplitude of the pSTR. Immunohistochemical analysis showed that DMF administration increased the immunoreactivity for Nrf2 and HO-1, a potent antioxidant enzyme, in RGCs immunolabeled with RNA-binding protein with multiple splicing (RBPMS). Immunoblotting analysis revealed an increase in the nuclear expression of Nrf2 and marked upregulation of HO-1 after DMF administration. These results suggest that DMF has survival-promoting effects in RGC after ONC, possibly via the Nrf2/HO-1 pathway. |
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Keywords: | dimethyl fumarate neuroprotection optic nerve crush retinal ganglion cells NF-E2-related factor 2 heme oxygenase-1 |
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