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Y. Kitaoka, Y. Munemasa, Y. Hayashi, S. Ueno; Involvement of Trx1 in Protective Effect of 17β-Estradiol Against TNF--Induced Axonal and Cell Body Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1446.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the effect of 17β-estradiol (E2) on the level of Trx1 in TNF--induced optic nerve degeneration. To evaluate the role of Trx1 in protective effect of E2 on RGC-5 cell death induced by TNF-.
Eight-week-old female Wistar 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- or PBS. The eyes were enucleated 1, 7, or 14 days after intravitreal injection. Furthermore, RGC-5 cell (gift from N. Agarwal) viability was tested after exposure to 10, 50, or 100ng/ml TNF- with or without glutamate. The effects of E2 (1 or 10 µM) and Trx1 siRNA were also evaluated. The expression of Trx1 in optic nerve or RGC-5 cells was examined by Western blot analysis. The localization of Trx1 in optic nerve cross section as well as transverse section was evaluated by immunohistochemistry.
Immunohistochemistry showed the substantial co-localization of Trx1 and neurofilament in the optic nerve. Morphometric analysis showed that E2 implantation significantly ameliorated TNF--induced axon loss. The level of Trx1 in the optic nerve was increased with E2 implantation. Cell viability assay showed that E2 treatment significantly improved the death of RGC-5 cells induced by TNF- and glutamate. This ameliorated effect was significantly inhibited by Trx1 siRNA transfection. The level of Trx1 in the RGC-5 cell was significantly increased with E2 treatment and this increase was ameliorated by Trx1 siRNA.
E2 can exert axonal and cell body protection against TNF--induced neurodegeneration with possible involvement of Trx1.
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