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Comparison of Topical Application of TSG-6, Cyclosporine, and Prednisolone for Treating Dry Eye

Kim, Yu Jeong MD; Ryu, Jin Suk MS; Park, Se Yeon DS; Lee, Hyun Ju DS; Ko, Jung Hwa MS; Kim, Mee Kum MD, PhD; Wee, Won Ryang MD, PhD; Oh, Joo Youn MD, PhD

doi: 10.1097/ICO.0000000000000756
Basic Investigation

Purpose: To compare the therapeutic effects of topical tumor necrosis factor (TNF)-α–stimulated gene/protein-6 (TSG-6) with those of cyclosporine and prednisolone eye drops in NOD.B10.H2b mice, a model for inflammation-mediated dry eye.

Methods: The 12-week-old NOD.B10.H2b mice were topically administered recombinant TSG-6 (0.1%) 4 times a day, 0.05% cyclosporine (Restasis) twice a day, or 1% prednisolone (Pred Forte) 4 times a day for 1 week. Aqueous tear production was measured by phenol red thread test, and corneal epithelial damage was observed with lissamine green and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Conjunctival goblet cell number was evaluated with periodic acid–Schiff staining. The levels of inflammatory cytokines were analyzed in the ocular surface (cornea and conjunctiva) and intraorbital gland. The dose-dependent effects of topical TSG-6 (0.001, 0.01, and 0.1%) were tested.

Results: Tear production and goblet cell density were significantly increased in all groups receiving TSG-6, cyclosporine, and prednisolone. Corneal epithelial staining was markedly reduced by TSG-6 and cyclosporine but not by prednisolone. In prednisolone-treated eyes, corneal epithelial thickness was decreased, and apoptosis of corneal epithelial cells was increased. The levels of interferon gamma and TNF-α in the ocular surface and intraorbital gland were significantly repressed by TSG-6 and cyclosporine, and prednisolone treatment significantly reduced the level of interferon gamma. The effects of TSG-6 on the ocular surface and tear production were dose dependent.

Conclusions: Topical TSG-6 was as effective in inflammation-mediated dry eye as cyclosporine eye drops. Topical prednisolone suppressed inflammation but induced apoptosis in the corneal epithelium.

*Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea; and

Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.

Reprints: Joo Youn Oh, MD, PhD, Department of Ophthalmology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea (e-mail:

Supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2014R1A2A1A11050895).

The authors have no conflicts of interest to disclose.

Received August 27, 2015

Received in revised form December 05, 2015

Accepted December 08, 2015

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