Activation of nuclear factor-kappaB during retinal degeneration in rd mice.
OBJECTIVE
Transcription factors of the nuclear factor-kappa beta (NF-kappaB) family have been demonstrated to play an important role in the regulation of gene expression in the chronic neurodegenerative disorders. The aims of the current study were to investigate the alteration of NF-kappaB activity during retinal degeneration in rd mice and further explore its role in photoreceptor apoptosis.


METHODS
Activation of NF-kappaB and its nuclear translocation in the retina of rd mice at postnatal days (P) 8, 10, 12, 14, 16, 18, and 28 were studied by immunohistochemical analysis using NF-kappaB P65 antibody. The amount of NF-kappaB P65 protein and NF-kappaB DNA-binding activity in the whole retina were assessed by western blot analysis and gel shift analysis, respectively. Expression of NF-kappaB in microglial cells labeled with CD11b was determined by double labeling.


RESULTS
NF-kappaB P65 nuclear translocation and its DNA binding activity started to increase in the rd retina at P10 and reached a peak at P12. Expressions of P65 remained at high levels from P12 to P18. Double labeling of P65 with CD11 at P14 showed colocalization of P65 in the microglial cells in the outer nuclear layer.


CONCLUSIONS
NF-kappaB was activated in the retinal degeneration of rd mice. NF-kappaB modulation may play a role in the retinal degeneration through microglial activation.
Peking University Eye Center, Peking University Third Hospital, Beijing, China.
Hui-Yang
HY
Zeng
Mark O M
MO
Tso
Shenghan
S
Lai
Hong
H
Lai
D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D016328:NF-kappa B; D004247:DNA