Topical TSG-6 Administration Protects the Ocular Surface in Two Mouse Models of Inflammation-Related Dry Eye

Invest Ophthalmol Vis Sci. 2015 Aug;56(9):5175-81. doi: 10.1167/iovs.14-16307.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules / administration & dosage*
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Dry Eye Syndromes / genetics
  • Dry Eye Syndromes / pathology
  • Dry Eye Syndromes / prevention & control*
  • Enzyme-Linked Immunosorbent Assay
  • Epithelium, Corneal / drug effects
  • Epithelium, Corneal / metabolism
  • Epithelium, Corneal / pathology*
  • Female
  • Gene Expression Regulation / drug effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Ophthalmic Solutions / administration & dosage
  • RNA / genetics
  • Real-Time Polymerase Chain Reaction
  • Recombinant Proteins / administration & dosage


  • Cell Adhesion Molecules
  • Cytokines
  • Ophthalmic Solutions
  • Recombinant Proteins
  • Tnfaip6 protein, mouse
  • RNA