Light-induced photoreceptor degeneration may involve the NFκB/caspase-1 pathway in vivo

Purpose: To determine the role of nuclear factor-κB (NFκB) in light-induced photoreceptor degeneration. Methods: Dark-adapted BALB/cJ mice, 4-8 weeks, were exposed to an intense green light (3.1-3.5 klux) for 1, 3, 6, 9, 12, or 24 h and killed immediately after exposure. The photoreceptor apoptosis was detected by TUNEL. Co-localization of NFκB p65 immunoreactivity and TUNEL in photoreceptor cells was detected by double immunolabeling. The protein levels of X-linked inhibitor of apoptosis protein (XIAP), Bcl-xL, caspase-1, and opsin after light exposure were analyzed by Western blot analysis. In addition, the initiation of NFκB activation was assessed by measuring the increase in phosphorylated IκBα (pIκBα). Immunohistochemical localization of caspase-1 was also performed on the mouse retinas. Results: Co-localization of NFκB p65 immunoreactivity with TUNEL was observed in scattered photoreceptor cells after 24 h of light exposure. The amount of pIκBα was increased after 1 h of light exposure, and in parallel, the amounts of XIAP and Bcl-xL were increased at 1 h. In contrast, caspase-1 did not increase until after 6 h of light exposure. Caspase-1-immunolabeling was observed in scattered photoreceptor cells after 3 h of light exposure but was markedly increased in many more cells at 6 h. Conclusions: These findings suggest that NFκB may play an anti-apoptotic role in the early response to light stress and that photoreceptor apoptosis induced by light stress may be mediated through an NFκB/caspase-1 pathway.