Molecule heals cornea from potentially-blinding infections from [email protected]

December 17, 2021

Researchers at the Wayne State University School of Medicine have published a major breakthrough in understanding how to heal a cornea infected with bacteria associated with contact lens infections.

Thymosin beta 4 is a novel corneal wound-healing therapy awaiting review by the U.S. Food and Drug Administration. Associate Professor of Ophthalmology, Visual and Anatomical Sciences Elizabeth Berger, Ph.D., is the principal investigator seeking to understand just how a molecule called thymosin beta 4 promotes corneal healing from microbial keratitis. The potentially-blinding infectious disease can cause corneal opacification and perforation. For the most part, antibiotics can clear the bacteria, but clinicians are often left to rely upon the eye’s innate ability to heal itself beyond this point.

“Our lab is working toward developing thymosin beta-4 (Tβ4) as a therapy to be used with antibiotics to further heal the eye after corneal infection,” Dr. Berger said. “To better understand how Tβ4 works, the current study looks at a key inflammatory cell, the macrophage, that is involved in the cornea’s response to infection. In this study, we show how Tβ4 regulates macrophage infiltration, activation and function to help restore corneal structure and function after infection.”

“Adjunctive Thymosin Beta-4 Treatment Influences MΦ Effector Cell Function to Improve Disease Outcome in Pseudomonas aeruginosa-Induced Keratitis,” is published in the International Journal of Molecular Sciences.

Her colleague, Gabriel Sosne, M.D., an associate professor of Ophthalmology, Visual and Anatomical Sciences and a corneal specialist, is the co-principal investigator.

The findings are especially important in developing Tβ4 for use in the clinical setting.

“This molecule is not just a wound-healing molecule, it influences key inflammatory cells to enhance inflammatory resolution. Further, this work highlights the off-target influence of antibiotics on the host response that extend beyond well-known bactericidal effects,” Dr. Berger said. “Adjunct Tβ4 treatment offers a more efficacious option for treating bacterial keratitis without the risks associated with steroids.”

The project sets the stage for future work regarding Tβ4, as well as the widely-used antibiotic ciprofloxacin. The researchers were surprised by the off-target effects of ciprofloxacin on the host response. “This antibiotic was found to be cytotoxic at concentrations used clinically and enhance activation of inflammatory macrophages,” Dr. Berger said.

They are now looking at the effects of adjunct Tβ4 treatment on PMNs, a type of immune cell that has granules (small particles) with enzymes that are released during infections, allergic reactions and asthma, and the major cellular infiltrate into the cornea following infection. “Most exciting, we are planning to submit a clinical trial for Tβ4 in the treatment of bacterial keratitis,” she said.

The Berger lab team of researchers included Ebrahim Abdul Shukkur, Ph.D.; lab manager Tommy Carion; graduate students Yuxin Wang and Ashten Stambersky; medical student Jeff Win; and undergraduate student Thanzeela Ebrahim.

“The collaboration with corneal specialist Dr. Sosne has been essential to developing this peptide as a treatment, as well. Everyone does a wonderful job in contributing to the success of this project,” Dr. Berger added.

The project is supported by awards R01 EY029836, P30 EY004068 and R01EY023226 from the National Eye Institute, and an unrestricted grant from Research to Prevent Blindness.

Molecule heals cornea from potentially-blinding infections from [email protected]
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