Application of topical tumor necrosis factor (TNF)-stimulated gene protein-6 (TSG-6) may be a suitable alternative to cyclosporine use in patients with inflammation-mediated dry eye, suggests a study published online in the journal Cornea.1 Previous research on the protein produced by mesenchymal stem/stromal cells within the body has indicated therapeutic effects in animal models of the heart, cornea, brain and other organs; however, further research and widespread clinical application remains limited due to production issues and variations in chemical stability.2,3 

In this investigation, researchers at Seoul National University Hospital in Korea divided NOD.B10.H2b-infected mice into four subgroups characterized by administration of one of four treatments for a period of seven days. The NOD.B10.H2b strain manifests clinical signs in mice similar to that of Sjögren’s syndrome in humans. 

Treatments included recombinant TSG-6 (i.e., 1μg in a 10μL phosphate buffered solution) QID, Restasis (0.05% cyclosporine ophthalmic emulsion, Allergan) BID, Pred Forte (1% prednisolone) QID and phosphate buffered solution QID. Currently, Restasis and Pred Forte are considered standards of inflammation-mediated dry eye treatment; however, certain immediate side effects, including ocular stinging and burning, as well as the longer-term issues associated with corticosteroid use, make these treatments somewhat controversial. An additional group of C57BL/6-infected mice was used for control purposes. 

At start, all NOD.B10.H2b mice exhibited similar decreased tear production in comparison with the control group; however, following the seven-day administration period, tear production of NOD.B10.H2b mice receiving the TSG-6, Restasis and Pred Forte treatments was markedly increased in comparison with that of the NOD.B10.H2b mice receiving phosphate buffered solution. All remained below that of the control group, however. Researchers also noted levels of proinflammatory cytokines TNF and INF were reduced following treatment with the three aforementioned applications. 

With respect to corneal staining, both the NOD.B10.H2b mice receiving TSG-6 and those receiving Restasis had decreased levels, while those receiving Pred Forte did not. 

“Together, data demonstrated that topical administration of 0.1% TSG-6 was as effective in improving signs of DED as 0.05% cyclosporine or 1% prednisolone ophthalmic solution,” the researchers say. “In addition, both TSG-6 and cyclosporine significantly reduced punctate corneal epithelial staining, but prednisolone did not.” These results suggest TSG-6 could be considered as a future dry eye treatment on par with cyclosporine; further study, however, on the effects of TSG-6 on dry eye parameters like tear film stability and tear osmolarity are necessary, as is investigation into mass production.   

1. Kim YJ, Ryu JS, Park SY, et al. Comparison of topical application of TSG-6, cyclosporine and prednisolone for treating dry eye. Cornea. 2016. [epub ahead of print]. 
2. Milner CM, Higman VA, Day AJ. TSG-6: a pluripotent inflammatory mediator? Biochem Soc Trand. 2006;34:446-50.
3. Prockop DJ. Concise review: two negative feedback loops place mesenchymal stem/stromal cells at the center of early regulators of inflammation. Stem Cells. 2013;31:2042-46.