Increased cGAS/STING signaling components in patients with Mooren's ulcer

  • Int J Ophthalmol. 2021 Nov 18;14(11):1660-1665. doi: 10.18240/ijo.2021.11.03.
Ya-Ni Zhang  1  2 ,  Yan-Ling Dong  3 ,  Wen-Pei Hao  4 ,  Xiao-Fei Bai  4 ,  Xia Qi  4 ,  Ting Liu  4 ,  Xiao-Tong Sun  3 ,  Chao Wei  4 ,  Xiao-Lin Qi  4  5
Affiliations
  • 1. Xi'an Children's Hospital, Xi'an 710004, Shaanxi Province, China.
  • 2. Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao 266071, Shandong Province, China.
  • 3. Qingdao Eye Hospital of Shandong First Medical University, Qingdao 266071, Shandong Province, China.
  • 4. State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao 266071, Shandong Province, China.
  • 5. Eye Hospital of Shandong First Medical University, Jinan 250021, Shandong Province, China.
PMID: 34804854 DOI: 10.18240/ijo.2021.11.03
Abstract

Aim: To explore the expression of cGAS/STING signaling components in Mooren's ulcer (MU).

Methods: Samples were obtained from ten MU patients, and eight residual corneal-scleral rings of healthy donor corneas for controls. Human corneal epithelial cells (HCECs) were used to evaluate the effect of cGAS/STING signaling pathway. Immunohistochemistry (IHC) and Western blot were used to examine the expression of cGAS, STING, and phosphorylated interferon regulatory factor 3 (p-IRF3) in MU tissues. The expression of interferon-β (IFN-β) and interferon-stimulated genes (ISGs) was quantified by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA).

Results: The protein levels of cGAS and STING in MU samples were significantly elevated when compared with the healthy controls by Western blot and IHC. After stimulation with cGAMP, Real-Time PCR and ELISA showed a dramatic increase of IFN-β and ISGs (containing CXCL10, IFIT1, and IL-6) in HCECs. Moreover, HCECs treated with cGAMP was characterized by increased phosphorylation and more nuclear translocation of IRF3. Meanwhile, increased p-IRF3 was observed in MU samples via IHC and Western blot.

Conclusion: The pronounced expression of cGAS/STING signaling components in the patients with MU and probably contribute to the onset and development of MU.

Keywords
Mooren's ulcer; cGAS/STING signaling; interferon regulatory factor 3; interferon-β.
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