Purchase this article with an account.
H. Lu, S. Li, F. X. Hu, W. Chen; Research of Tlr4-myd88 Dependent Pathway in Endotoxin-Induced Uveitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1172.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The research of TLR4-MyD88 dependent pathway in Endotoxin-induced UvitisHong Lu, Shang Li, Xiaofeng Hu,Wei ChenDepartmnet of Ophthalmology, Beijing Chaoyang Hospital, Capital MedicalUniversity, No. 8 Baijiazhuang Road, Chaoyang District, Beijing, China, 100020;
To investigate the dynamics and distribution of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B p65 (NF-ΚB p65) and resident tissue macrophages in iris-ciliray tissue during endotoxin-induced uveitis (EIU) in Wistar rats.
Wistar rats were randomly divided into 5 groups(0h, 12h, 24h, 48h and 72, n=10/ group). Animal model of EIU was established by a hind footpad injection of 200µg Cholera vibrio LPS in four groups (12h, 24h, 48h and 72) except 0h group (control group). Expression of TLR4, MyD88 and NF-ΚB p65 in iris ciliary body tissue was detected through immunohistochemical staining. Immunohistochemical localization of TLR4 and a resident tissue macrophage marker, cluster of differentiation 163 (CD163), was performed on whole mount isolated iris-ciliary body complexes. The distribution patterns and phenotypes of TLR4 and CD163 were further characterized by double-labeled immunofluorescence studies.
TLR4, MyD88 and NF-ΚB p65 were detectable in the iris stroma12 h after injection, and the number significantly increased 24, 48 h and decreased gradually 72 hours after injection (p<0.001 by one-way ANOVA). The morphology of these cells hardly changed 12-72 h after injection. CD163 was expressed in the uvea in all rats.During the inflammatory response phase (0-48 h after injection), the proportion of CD163 tissue macrophages having a round morphology increased concurrently with a decrease in the proportion of dendritiform CD163 cells (p<0.001 by one-way ANOVA). These changes occurred mainly in the macrophages located in the stroma bordering the iris endothelial layer. Double-labeling immunofluorescence demonstrated the co-expression of TLR4 and CD163 in round stroma cells with TLR4 located at the cell membrane and CD163 in the cytoplasm.
The increased expression of TLR4 and its downstream signal transduction molecules MyD88, NF-ΚB p65 indicate the potential role of TLR4-MyD88 dependent pathway in the pathogenesis of acute anterior uveitis (AAU). This has significant implications for the understanding of ocular inflammation and for interpreting the potential role of Gram-negative bacteria in the pathogenesis of acute anterior uveitis.Key wordsEIU, TLR4, CD163,MyD88, NF-ΚB p65.
This PDF is available to Subscribers Only