The Link module of human TSG-6 (Link_TSG6) promotes wound healing, suppresses inflammation and improves glandular function in mouse models of Dry Eye Disease

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Joo Youn Oh
  • Jin Suk Ryu
  • Hyeon Ji Kim
  • Rebecca J. Dodd
  • Se Hyun Choi
  • Yu Jeong Kim

Abstract

Purpose
To investigate the potential of the Link_TSG6 polypeptide comprising the Link module of human TSG-6 (TNF-stimulated gene/protein-6) as a novel treatment for dry eye disease (DED).

Methods
We analyzed the therapeutic effects of topical application of Link_TSG6 in two murine models of DED, the NOD.B10.H2b mouse model and the desiccating stress model. The effects of Link_TSG6 on the ocular surface and DED were compared with those of full-length TSG-6 (FL_TSG6) and of 0.05% cyclosporine (Restasis®). Additionally, the direct effect of Link_TSG6 on wound healing of the corneal epithelium was evaluated in a mouse model of corneal epithelial debridement.

Results
Topical Link_TSG6 administration dose-dependently reduced corneal epithelial defects in DED mice while increasing tear production and conjunctival goblet cell density. At the highest dose, no corneal lesions remained in ∼50% of eyes treated. Also, Link_TSG6 significantly suppressed the levels of inflammatory cytokines at the ocular surface and inhibited the infiltration of T cells in the lacrimal glands and draining lymph nodes. Link_TSG6 was more effective in decreasing corneal epithelial defects than an equimolar concentration of FL_TSG6. Link_TSG6 was significantly more potent than Restasis® at ameliorating clinical signs and reducing inflammation. Link_TSG6 markedly and rapidly facilitated epithelial healing in mice with corneal epithelial debridement wounds.

Conclusion
Link_TSG6 holds promise as a novel therapeutic agent for DED through its effects on the promotion of corneal epithelial healing and tear secretion, the preservation of conjunctival goblet cells and the suppression of inflammation.

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Keywords
Dry eye diseaseLink_TSG6Link moduleTNF-Stimulated gene/protein-6TSG-6

Bibliographical metadata

Original languageEnglish
Pages (from-to)40-50
JournalThe ocular surface
Volume24
Early online date27 Dec 2021
DOIs
Publication statusPublished - 1 Apr 2022