Light-induced photoreceptor degeneration may involve the NF kappa B/caspase-1 pathway in vivo.
OBJECTIVE
To determine the role of nuclear factor-kappaB (NFkappaB) 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 NFkappaB 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 NFkappaB activation was assessed by measuring the increase in phosphorylated IkappaBalpha (pIkappaBalpha). Immunohistochemical localization of caspase-1 was also performed on the mouse retinas.


RESULTS
Co-localization of NFkappaB p65 immunoreactivity with TUNEL was observed in scattered photoreceptor cells after 24 h of light exposure. The amount of pIkappaBalpha 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 NFkappaB 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 NFkappaB/caspase-1 pathway.
Wu
Tinghuai
T
Wilmer Eye Institute, Johns Hopkins Hospital, 600 N. Wolfe Street, Woods # 457, Baltimore, MD 21287-9238, USA.
Chiang
Samuel K S
SK
Chau
Felix Y
FY
Tso
Mark O M
MO
D000818:Animals; D020170:Caspase 1 / Q000032:analysis / Q000502:physiology*; D003623:Dark Adaptation / Q000502:physiology; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000032:analysis / Q000502:physiology*; D009410:Nerve Degeneration / Q000201:enzymology*; D018696:Neuroprotective Agents / Q000032:analysis / Q000378:metabolism*; D010775:Photic Stimulation / Q000009:adverse effects*; D020419:Photoreceptor Cells, Vertebrate / Q000737:chemistry / Q000201:enzymology*; D015398:Signal Transduction / Q000502:physiology*
D016328:NF-kappa B; D018696:Neuroprotective Agents; D020170:Caspase 1