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Y. Hayashi, Y. Kitaoka, H. Takeda, H. Fujino, Y. Munemasa, J. Kogo, K. Kuribayashi, R. Ohtani-Kaneko, K. Hirata, S. Ueno; Neuroprotective Effect of 17ß-Estradiol Against TNF- Induced Axonal Degeneration and p-ERK Expression. Invest. Ophthalmol. Vis. Sci. 2007;48(13):634.
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We previously reported neuroprotective effect of 17ß-estradiol (E2) through phosphorylation of extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway in NMDA-induced retinal neurotoxicity. The purpose of present study is to investigate the change in p-ERK levels in both retina and optic nerve and whether E2 exerts a neuroprotective effect in TNF-α induced axonal 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 10ng TNF-α. The eyes were enucleated at 1 and 14 days and 2 months after injection. Expression of p-ERK was examined by Western blot analysis at 1 and 14 days after injection. The localization of p-ERK on TNF-α treated optic nerve was evaluated by immunohistochemistry. Moreover, axon number was evaluated by staining with p-phenylenediamine of the optic nerve cross section 14 days after injection.
Western blot analysis showed the decrease of p-ERK protein level in the optic nerve 1 and 14 days after injection. Immunoreactivity of p-ERK was detected in the glial cells in the retina and optic nerve. Axon number in the optic nerve was decreased 14 days after TNF-α injection and the pretreatment of E2 prevented TNF-α-induced axonal loss.
Since we observed that E2 induced up-regulation of p-ERK in the retina, we speculate that p-ERK may play a pivotal role in neuroprotective effect of E2 against TNF-α induced axonal degeneration.
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