June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
IL-37 prevents corneal barrier disruption by inhibiting TNF-α/CTSS signaling in primary human corneal epithelial cells under hyperosmotic stress
Author Affiliations & Notes
  • De-Quan Li
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Yun Zhang
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
    Eye Hospital, School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • Jinmiao Li
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
    Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • Xin Chen
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
    Eye Hospital, School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • Stephen C Pflugfelder
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Cintia S De Paiva
    Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   De-Quan Li Allergan, plc., Code F (Financial Support); Yun Zhang None; Jinmiao Li None; Xin Chen None; Stephen Pflugfelder Allergan, plc., Code F (Financial Support); Cintia De Paiva None
  • Footnotes
    Support  NIH NEI Grants EY023598 (DQL), EY011915 (SCP) and EY030447 (CDP), Core Grant for Vision Research EY002520, Allergan Inc., Research to Prevent Blindness, Oshman Foundation.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1977 – A0307. doi:
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    • Get Citation

      De-Quan Li, Yun Zhang, Jinmiao Li, Xin Chen, Stephen C Pflugfelder, Cintia S De Paiva; IL-37 prevents corneal barrier disruption by inhibiting TNF-α/CTSS signaling in primary human corneal epithelial cells under hyperosmotic stress. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1977 – A0307.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To explore novel role and molecular mechanism of a natural anti-inflammatory cytokine interleukin (IL) 37 in preventing corneal epithelial barrier disruption from hyperosmolar stress as occurs in dry eye.

Methods : Primary human corneal epithelial cells (HCECs) were cultured from fresh donor limbal explants. An in vitro dry eye model with hyperosmolar stress was established by switching HCECs from isosmolar (312mOsM) to hyperosmolar medium (350-500 mOsM) alone or with rhIL-37, some cells were treated with TNF-α, for different periods (2-48 hours). The expression of cytokines and cathepsin S, and barrier protein integrity were evaluated by RT-qPCR, ELISA, and immunofluorescent staining with confocal microscopy.

Results : The integrity of epithelial barrier was significantly disrupted in HCECs exposed to hyperosmolar medium, as shown by immunofluorescent images of tight junction (ZO-1, occludin and claudin-1) and adheren junction (E-cadherin) proteins. The opposite responses were observed between TNF-α stimulated and IL-37 suppressed in HCECs exposed to hyperosmolarity. Cathepsin S, encoded by CTSS gene, was found to directly disrupt epithelial barrier. Interestingly, CTSS expression was significantly induced by TNF-α and hyperosmolarity, while exogenous rhIL-37 inhibited TNF-α and CTSS expression at mRNA and protein levels following hyperosmolar stress. rhIL-37 further restored barrier protein integrity, observed in 2D and 3D confocal immunofluorescent images, in HCECs under hyperosmolar stress.

Conclusions : Our findings demonstrate a novel signaling pathway by which the anti-inflammatory cytokine IL-37 suppresses TNF-α and CTSS stimulated corneal epithelial barrier disruption under hyperosmotic stress. This study provides new insight into mechanisms disrupting or preventing corneal barrier in dry eye disease.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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