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Topical TSG-6 administration protects the ocular surface in two mouse models of inflammation-related dry eye

Cited 32 time in Web of Science Cited 33 time in Scopus
Authors

Lee, Min Joung; Kim, Dong Hyun; Ryu, Jin Suk; Ko, Ah Young; Ko, Jung Hwa; Kim, Mee Kum; Wee, Won Ryang; Khwarg, Sang In; Oh, Joo Youn

Issue Date
2015-01
Publisher
Association for Research in Vision and Ophthalmology
Citation
Investigative Ophthalmology and Visual Science, Vol.56 No.9, pp.5175-5181
Abstract
PURPOSE. To investigate the therapeutic potential of TNF-alpha stimulated gene/protein (TSG)-6 in two mouse models of inflammation-mediated dry eye syndrome (DES). METHODS. We created inflammation-mediated DES in mice by injecting concanavalin A (ConA; 10 mg/mL) into intraorbital and extraorbital lacrimal glands. Recombinant TSG-6 (1 mu g in phosphate-buffered solution [PBS]) or the same volume of PBS was administered topically to eyes of the mice four times a day (QID) for 1 week. In parallel experiments, we topically applied TSG-6 (1 mu g) or PBS QID to eyes of 12-week-old NOD.B10.H2(b) mice, a model for primary Sjogren's syndrome. Seven days later, tear production was measured, and the corneal surface was observed for epithelial defects. The number of goblet cells was evaluated in the forniceal conjunctiva. The levels of proinflammatory cytokines were analyzed in the cornea, conjunctiva, and lacrimal glands. Also, in vitro experiments were performed using cultures of corneal epithelial cells (CECs) to test the effects of TSG-6 on cell proliferation and migration. RESULTS. Topical TSG-6 administration improved tear production and reduced corneal epithelial defects both in ConA-injected mice and NOD.B10.H2(b) mice. The conjunctival goblet cell density was higher in TSG-6-treated eyes than in PBS-treated eyes. The expression of proinflammatory cytokines in the cornea, conjunctiva, and intraorbital gland was repressed by TSG-6, while the levels of proinflammatory cytokines in the extraorbital gland were not changed. In vitro experiments revealed that TSG-6 promoted the migration of CECs, but did not affect the proliferation. CONCLUSIONS. Topical TSG-6 protected the ocular surface by suppressing inflammation and promoting corneal epithelial wound healing.
ISSN
0146-0404
URI
https://hdl.handle.net/10371/202944
DOI
https://doi.org/10.1167/iovs.14-16307
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  • College of Medicine
  • Department of Medicine
Research Area 각막 및 외안부 질환, 백내장

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