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Y. Kitaoka, Y. Kitaoka, A.A. Sadun, J. Wang, F.N. Ross–Cisneros, T.T. Lam; Enhanced expression of NF–kappa B p65 protein in TNF–alpha–induced optic nerve degeneration . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1611.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: AIDS–related optic neuropathy is linked to TNF–α induced optic neuropathy. To investigate the mechanism of these related optic neuropathies, we examined the involvement of NF–kappa B p65, a transcription factor that is reported to be important in neuronal degeneration and/or survival, in TNF–alpha–induced optic nerve degeneration. Methods: Intravitreal injections of TNF–alpha (0.1–10 ng) or its vehicle were given in adult male Lewis albino rats. Semi–thin sections of optic nerve at 2 weeks after injection were evaluated morphologically by light microscopy. Immunohistochemistry with antibody against myelin basic protein was used as a marker of myelin. NF–kappa B p65 protein was estimated and localized in the optic nerve at 1 day after injection by using Western blot analysis and immunohistochemistry respectively. Results: Compared to the control, TNF–alpha–treated optic nerve had diffuse and substantial axonal degeneration showing loss of myelin as demonstrated by immunohistochemistry of myelin basic protein, some large pale and mottled axons and loss of axons by Richardson staining and p–phenylenediamine staining of optic nerve sections. Both Western blotting and immunostaining of NF–kappa B p65 demonstrated its presence in normal retina and optic nerve, and a transient increase after TNF–alpha injection in the optic nerve but not in the retina. Conclusions: There is an early and transiently enhanced expression of NF–kappa B p65 in rat optic nerve but not in the retina in TNF–alpha induced optic neuropathy. These findings suggest that NF–kappa B p65 may be involved in the pathophysiology of TNF–alpha–mediated optic neuropathy.
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