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Updated: Apr 5, 2026
Induction of Ocular Surface Inflammation and Collection of Involved Tissues
Published on: August 4, 2022
Topical TSG-6 Administration Protects the Ocular Surface in Two Mouse Models of Inflammation-Related Dry Eye
Min Joung Lee1, Dong Hyun Kim2, Jin Suk Ryu3
1Department of Ophthalmology, Hallym University Sacred Heart Hospital, Anyang, Korea.
Purpose:
To investigate the therapeutic potential of TNF-α 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 μg 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 μg) or PBS QID to eyes of 12-week-old NOD.B10.H2b mice, a model for primary Sjögren'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.H2b 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.
Insights
Topical Tumor Necrosis Factor-alpha Stimulated Gene/Protein 6 (TSG-6) therapy improved dry eye symptoms in mouse models. TSG-6 treatment reduced ocular inflammation and enhanced corneal healing.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Dry eye syndrome (DES) is a prevalent ocular surface disease characterized by inflammation.
- Current treatments for DES have limitations, necessitating the exploration of novel therapeutic agents.
- Tumor Necrosis Factor-alpha Stimulated Gene/Protein 6 (TSG-6) is an anti-inflammatory protein with potential therapeutic applications.
Purpose of the Study:
- To evaluate the efficacy of topical TSG-6 in ameliorating inflammation and promoting ocular surface repair in two distinct mouse models of dry eye syndrome.
- To investigate the impact of TSG-6 on tear production, corneal integrity, goblet cell density, and inflammatory cytokine expression.
- To assess the in vitro effects of TSG-6 on corneal epithelial cell proliferation and migration.
Main Methods:
- Two mouse models of inflammation-mediated DES were established: concanavalin A (ConA) injection into lacrimal glands and the NOD.B10.H2b model for Sjögren's syndrome.
- Recombinant TSG-6 or vehicle (PBS) was administered topically to the eyes four times daily for one week.
- Ocular surface parameters including tear production, corneal epithelial defects, goblet cell density, and cytokine levels were analyzed. In vitro assays assessed corneal epithelial cell behavior.
Main Results:
- Topical TSG-6 significantly improved tear production and reduced corneal epithelial defects in both DES models.
- TSG-6 treatment led to increased goblet cell density in the conjunctiva.
- TSG-6 suppressed proinflammatory cytokine expression in ocular tissues and promoted corneal epithelial cell migration in vitro.
Conclusions:
- Topical TSG-6 demonstrates significant therapeutic potential for dry eye syndrome by mitigating ocular surface inflammation.
- TSG-6 promotes corneal epithelial wound healing, suggesting a role in ocular surface repair mechanisms.
- TSG-6 represents a promising novel therapeutic strategy for managing inflammation-mediated dry eye disease.
