Purchase this article with an account.
T. Wu, S. Chiang, M. Tso; The Lack of the p50 Subunit of NF-kB Increases the Vulnerability of Photoreceptor Cells to Light Stress . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5127.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Nuclear factor-(NF)kB (p50/p65) is a transcription factor that may play a neuroprotective role in light-induced photoreceptor degeneration. Our previous studies have demonstrated that light activates NF-kB in photoreceptor cells and that the light-induced photoreceptor degeneration may be mediated by NF-kB/caspase-1 pathway in vivo. To determine the specific role of NF-kB in light-induced photoreceptor apoptosis, we examined the effects of NF-kB on light-induced photoreceptor degeneration using p50 knockout mice (p50-/-mice) as a means of the inhibition of NF-kB activity. Methods: The histology of the retinas of the p50-/- and control mice (aged 4- to 8-weeks) was examined. The NF-kB DNA-binding activity in the retinas was determined by electrophoretic mobility shift assay (EMSA). After the p50-/- mice were exposed to an intense green light (3.1 to 3.5 Klux) for 1 h, followed by 24 h of dark recovery, the light-induced photoreceptor apoptosis was determined by TUNEL assay. To further study DNA-binding activities of NFkB-related transcription factors in the retinas of the p50-/- mice, protein/DNA arrays were performed. Results: The retinas of the p50-/- mice were histologically normal. NF-kB binding activity in the p50-/- mice was dramatically decreased, as compared to that in control mice. The light-induced photoreceptor apoptosis in the p50-/- mice was significantly increased after l h of light exposure. The DNA-binding activity of activator protein 1(AP-1) in the nuclear extracts was higher in the p50-/- mice as compared to that in control mice.Conclusions: The lack of NF-kB activity in the retinas of the p50-/-mice increases the vulnerability of photoreceptor cells to light stress, which may be caused by the increased activity of AP-1 in the photoreceptor cells of these transgenic mice. These observations may suggest that NF-kB plays a neuroprotective role in light-induced photoreceptor degeneration.
This PDF is available to Subscribers Only