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Invest Ophthalmol Vis Sci. 2015 Aug;56(9):5110-7. doi: 10.1167/iovs.15-16890.

Primary Mechanisms of Thymosin β4 Repair Activity in Dry Eye Disorders and Other Tissue Injuries.

Author information

1
Departments of Ophthalmology and Anatomy and Cell Biology Kresge Eye Institute, Wayne State University School of Medicine, Detroit, Michigan, United States.
2
Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine, Washington, DC, United States.

Abstract

Dry eye disorders are becoming more common due to many causes, including an aging population, increased pollution, and postrefractive surgery. Current treatments include artificial tears; gels; lubricants; tear duct plugs; and anti-inflammatory agents such as steroids, doxycycline, and cyclosporine. For more severe forms of the disease, serum tears and scleral contact lenses are employed. Despite these therapies, successful resolution of the problem is limited because none of these treatments fully addresses the underlying causes of dry eye to promote ocular surface repair. Thymosin β4 (Tβ4), a small, naturally occurring protein, promotes complete and faster corneal healing than saline alone or prescription agents (doxycycline and cyclosporine) in various animal models of eye injury. In human trials, it improves both the signs and symptoms of moderate to severe dry eye with effects lasting beyond the treatment period. This review will cover the multiple activities of Tβ4 on cell migration, inflammation, apoptosis, cytoprotection, and gene expression with a focus on mechanisms of cell migration, including laminin-332 synthesis and degradation, that account for this paradigm-shifting potential new treatment for dry eye disorders. We will also speculate on additional mechanisms that might promote eye repair based on data from other tissue injury models. Such studies provide the rationale for use of Tβ4 in other types of eye disorders beyond dry eye. Finally, we will identify the gaps in our knowledge and propose future research avenues.

PMID:
26241398
DOI:
10.1167/iovs.15-16890
[Indexed for MEDLINE]

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