Corneal NF-κB activity is necessary for the retention of transparency in the cornea of UV-B-exposed transgenic reporter mice

To determine the dynamics of Nuclear Factor-kappa B (NF-kappa B) in murine cornea] pathology and the role of NF-kappa B in maintaining corneal clarity after ultraviolet B radiation insult, transgenic mice containing NF-kappa B-luciferase reporter were exposed to LPS (bacterial lipopolysaccharide), TNF-kappa (Tumor Necrosis Factor-alpha) or 4 kJ m(-2) UV-B radiation. NF-kappa B decoy oligonucleotides were also administered in some of the UV-B experiments. Following various exposure times, the mice were sacrificed and whole eyes or corneal tissues were obtained. Whole eyes were examined for scattering using a point-source optical imaging technique. Tissue homogenates were examined for luciferase activity using a luminometer. TNF-alpha and LPS-injected NF-kappa B-luciferase transgenic mice demonstrated 3-10-fold increases in cornea NF-kappa B with peak activities at 4 and 6 hr post-injection, respectively. Mice exposed to 4 kJ m(-2) UV-B exhibited a 3-fold increase in NF-kappa B activity 4 hr post-exposure. The administration of NF-kappa B-decoy oligonucleotides to mice had the effect of reducing UV-13-induced NF-kappa B activity in the cornea and significantly increasing the amount of light scattering in UV-B exposed corneas 7 days post-UV-B exposure when compared to sham injected mice. These results indicate that NF-kappa B is activated in cornea in pathologies that involves increased plasma levels of LPS and TNF-alpha, as well as direct UV-B exposure, and suggest that NF-kappa B activation play an essential part in the corneal healing process. (c) 2005 Elsevier Ltd. All rights reserved.