Thymosin β4 significantly reduces the signs of dryness in a murine controlled adverse environment model of experimental dry eye

Abstract

Objective: Dry eye syndrome is a common condition that affects up to 20% of the population aged 45 and older. There are no successful treatments to date. The goal of this research was to determine the efficacy of various doses and the optimal frequency of thymosin β4 (Tβ4) treatment in a murine severe dry eye model.

Research design and methods: The study was performed using a controlled adverse environment chamber (CAE) in combination with scopolamine to induce moderate to severe dry eye in mice. The study included five mice per group and tested six different doses of Tβ4 twice per day for 12 days. Tβ4 at 0.1% was also administered 2 – 4 times per day for 12 days. Healing was measured by fluorescein staining.

Main outcome measures: Tβ4 significantly reduced the signs of dry eye relative to controls. The treatment effect was more pronounced than the positive controls, doxycycline and Restasis (cyclosporine 0.05%). Active doses of 0.1 and 0.5% were determined, and it was found that the frequency of dosing at 2 times per day was the most effective for healing.

Conclusions: Tβ4 has the potential to be an important new effective therapeutic for dry eye.

Keywords:

• controlled adverse environment
• cornea
• dry eye syndrome
• fluorescein staining
• signs of dry eye
• thymosin β4

Acknowledgments

We would like to thank David Crockford and Dr Christian B Allan for their help in the preliminary design of the study and drug formulation, respectively. We would also like to thank George W Ousler at ORA, Inc., Andover, MA for advice on the animal protocol. This study was performed by ORA, Inc.

Declaration of ineterest

This paper is part of a supplemental issue, sponsored by SciClone. Work was supported by RegeneRx Biopharmaceuticals, Inc. as part of preclinical data needed for a clinical trial. The sponsor read the paper and made minor edits. GS and HK are consultants for RegeneRx Biopharmaceuticals, Inc. but neither owns any stock. George W Ousler and staff at ORA, Inc. did the data analysis and preparation of figures. David Crockford at RegeneRx did some of the statistical design and Christian Allan at RegeneRx was involved in drug formulation. C. Kim has no conflict of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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