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Y. Hayashi, Y. Kitaoka, H. Takeda, H. Fujino, S. Ueno; Involvement of ER in Protective Effect of 17β-Estradiol Against TNF--Induced Optic Nerve Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4938. doi: https://doi.org/.
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We previously reported the neuroprotective effect of 17β-estradiol (E2) through phosphorylation of extracellular signal-regulated kinase (ERK) /mitogen-activated protein kinase (MAPK) pathway in TNF-α-induced axonal degeneration. The purpose of present study is to investigate the change in estrogen receptor α (ERα) expression and its relationship to the axon death in TNF-α-induced optic nerve degeneration.
Eight-week-old female and male Wistar rats were used as subjects. Female rats were divided into sham operated and ovariectomized (OVX) groups. The OVX rats were treated with either solvent vehicle or E2 subcutaneous implant immediately after ovariectomy. At 14 days post-operation, all rats were received intravitreal injection of 10 ng TNF-α or PBS. The eyes were enucleated 1, 7, or 14 days after intravitreal injection. The expression of ERα was examined by Western blot analysis. The localization of ERα in optic nerve cross section as well as transverse section was evaluated by immunohistochemistry.
Western blot analysis and immunohistochemistry showed the existence of ER in the optic nerve. They were co-localized with neurofilament, but not with vimentin in the optic nerve from normal subjects. There was a significant decrease in ERα protein level in the optic nerve 14 days after TNF-α injection. Substantial decrease in neurofilament immunoreactivity was observed in TNF-α-treated eyes with vehicle implantation and this depletion was ameliorated by E2 implantation.
Existence of ERα in axon and close relationship between ERα and neurofilament suggest that E2 can exert direct axonal protection without cell body involvement against TNF-α-induced axonal degeneration.
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