한빛사 논문
Joo Youn ha,b,*, Jin Suk Ryub, Hyeon Ji Kimb, Nikolaos Kouvatsosc,d, Rebecca J. Doddc,d, Se Hyun Choib, Yu Jeong Kimb, Caroline M. Milnerd,e, Anthony J. Dayc,d,e,*
aDepartment of Ophthalmology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea
bLaboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea
cWellcome Trust Centre for Cell-Matrix Research, United Kingdom
dDivision of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences and Manchester M13 9PT, United Kingdom
eLydia Becker Institute of Immunology and Inflammation, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, M13 9PT, United Kingdom
*Corresponding author.
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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