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Joo Youn Oh, Yujeong Kim, Jin Suk Ryu, Se Yeon Park, Hyun Ju Lee, Jung Hwa Ko; Comparison of Topical TSG-6, Cyclosporine and Prednisolone for Treatment of Inflammation-related Dry Eye in NOD.B10.H2b Mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1449. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Our group has previously shown that topical administration of TNFα-stimulated gene/protein 6 (TSG-6) protected the ocular surface and improved lacrimal production in mouse models of inflammation-related dry eye (Invest Ophthalmol Vis Sci. 2015;56:5175-81). We performed the present study for two purposes: 1) to compare the effects of topical TSG-6 in a mouse model of DES with those of 1% prednisolone and 0.05% cyclosporine eye drops, and 2) to investigate the dose-response relationship of topical TSG-6 in improving DES.
The 12-week-old NOD.B10.H2b mice received topical administration of recombinant TSG-6 (0.1%) QID, 0.05% cyclosporine (Restasis®) BID or 1% prednisolone (Pred forte®) QID for one week. Aqueous tear production was measured by phenol red thread test, and corneal epithelial damage was observed with lissamine green and TUNEL staining. Conjunctival goblet cell density was evaluated by PAS (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 also tested.
Tear production and goblet cell density were significantly increased in all groups receiving TSG-6, cyclosporine and prednisolone. Corneal epithelial damage was markedly reduced by TSG-6 and cyclosporine, but not by prednisolone. In prednisolone-treated eyes, corneal epithelial thickness was decreased, and the apoptosis of corneal epithelial cells was increased. The levels of IFN-γ 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 IFN-γ. The effects of TSG-6 on the ocular surface and tear production were dose-dependent.
Topical TSG-6 was as effective in an inflammation-mediated dry eye as cyclosporine eye drops. Topical prednisolone showed anti-inflammatory effects, but induced apoptosis in the corneal epithelium.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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