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Hong Lu, Jing Wang, Xiaofeng Hu, Wei Chen, Zhuozai Xu, Shang Li, Yingzhi Xu; Nuclear Factor Translocation and Acute Anterior Uveitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2270.
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To investigate toll- like receptor 4-mediated signal transduction in the development of acute anterior uveitis.
Establish animal models with acute anterior uveitis by intraperitoneal injection of vibrio cholera endotoxin into C3H /HeN mice (wild type) and C3H /HeJ mice (TLR4 gene defection type). Peritoneal macrophages were obtained from C3H/HeN and C3H/HeJ mice. Immunofluorescence staining was used to observe the expression of TLR4, MyD88, and NF-ΚB,with or without LPS (1 µg/ml). To investigate the importance of TLR4 in the signal pathway, a group, blocked by anti-TLR4 antibody before LPS stimulation, was added to theC3H/HeN mice sample.
In vitro, in C3H/HeN mice, Iris posterior synechia was found 24 hours later. However, an inflammation reaction was not found in the anterior chamber of the C3H /HeJ mice. In the cell culture of the C3H / HeN mice , TLR4 was primarily expressed in the membrane and no significant difference in inflorescence intensity (p = 0.081) was found among the groups. MyD88 was expressed in the cytoplasm and the nucleus. There is statistical significance in the fluorescence intensity among groups of C3H/HeN mice (F = 393.485, p < 0.0001). NF-ΚB was primarily expressed in the cytoplasm before LPS stimulation. However, this occurred 1 hour after LPS stimulation and could be observed in the nucleus. Six hours after LPS stimulation, the expression of NF-ΚB could not be detected in the cytoplasm or the nucleus. The fluorescence intensity of TLR4,MyD88 expression showed no significant difference (p = 0.113) between the anti-TLR4 antibody pretreatment group and the other groups of C3H/HeN mice. However, in the anti-TLR4 antibody pretreatment group, 1h to 24h after LPS stimulation, NF-ΚB only expressed in the cell membrane. Macrophages from all groups of C3H / HeJ mice showed no obvious changes in morphology and size after LPS stimulation (p = 0.257). TLR4 was primarily expressed in the cell membrane, and fluorescence intensity showed no statistical significance (p = 0.228); MyD88 was expressed in the cytoplasm and the nucleus ; NF- ΚB was expressed in the cytoplasm, with LPS stimulation; however, 1h after LPS stimulation, it appeared in the cell membrane and persisted until 24h .
Acute anterior uveitis can be induced in C3H/HeN mice, but it cannot be induced in the C3H/HeJ mice. The variation of expression of TLR4,MyD88, NF-ΚB after LPS stimulation in vitro, indicated the potential role of a TLR4-MyD88-dependent pathway in the pathogenesis of acute anterior uveitis. The blockage of this pathway by anti-TLR4 may signal a new direction in the treatment of acute anterior uveitis.
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