Purchase this article with an account.
Mayumi Ueta, Hiromi Nishigaki, Katsuhiko Shinomiya, Norihiko Yokoi, Chie Sotozono, Shigeru Kinoshita; IKZF1 Expression and Upregulation by polyI:C in Human Ocular Surface Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3858.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) are acute inflammatory vesiculobullous reactions of the skin and mucosa, such as the ocular surface and oral cavity. In genome wide association study (GWAS), we found the association between IKAROS Family Zinc Finger 1 (IKZF1) and Cold medicine related SJS/TEN with severe ocular complication (CM-SJS/TEN with SOC). Ikaros is a transcription factor which regulates numerous biological events, but the function of it was reported only in the immune cells such as lymphocytes. On the other hands, we have suggested that epithelium might be contribute to the pathobiology of CM-SJS/TEN with SOC, because EP3, the protein of PTGER3, which SNPs significantly associated with CM-SJS/TEN with SOC, was dominantly expressed on the ocular surface epithelium and EP3 on the epithelium negative regulated ocular surface inflammation. Furthermore, we also reported that TLR3, which SNPs significantly associated with CM-SJS/TEN with SOC in Japanese, also strongly expressed on the ocular surface epithelium and TLR3 positively regulated ocular surface inflammation.In this study, we examined the expression of IKZF1 in the human ocular surface (conjunctival and corneal) epithelial cells, and investigated whether it could be upregulated by TLR3 ligand.
For quantitative RT-PCR, primary human conjunctival epithelial cells were harvested from conjunctival tissue obtained at conjunctivochalasis surgery and cultured using the previously described method. Primary human corneal cells were harvested from the rest of the limbus of import donor cornea tissue after using for corneal transplantation. For RT-PCR and immunohistology, conjunctival tissue obtained at conjunctivochalasis surgery was used.
We found that human conjunctival epithelium expressed IKZF1 mRNA by RT-PCR and using quantitative RT-PCR, we found that it could be upregulated by TLR3 ligand, polyI:C. We also found that IKZF1 mRNA expression in corneal epithelial cells could be upregulated by polyI:C. Immunohistology showed that IKZF1 protein also expressed in conjunctival epithelium as same as CD3 positive T cells.
Our results might suggest that IKZF1 in the ocular surface could contribute to the ocular surface inflammation in the SJS/TEN.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
This PDF is available to Subscribers Only