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
- Authors
- Oh, Joo Youn; Ryu, Jin Suk; Kim, Hyeon Ji; Kouvatsos, Nikolaos; Dodd, Rebecca J.; Choi, Se Hyun; Jeong, Kim Yu; Milner, Caroline M.; Day, Anthony J
- Issue Date
- Apr-2022
- Publisher
- ELSEVIER
- Keywords
- Dry eye disease; Link_TSG6; Link module; TNF-Stimulated gene/protein-6; TSG-6
- Citation
- OCULAR SURFACE, v.24, pp.40 - 50
- Indexed
- SCIE
SCOPUS
- Journal Title
- OCULAR SURFACE
- Volume
- 24
- Start Page
- 40
- End Page
- 50
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/189149
- DOI
- 10.1016/j.jtos.2021.12.012
- ISSN
- 1542-0124
- 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.H2(b) 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 (R)). 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 similar to 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 (R) 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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