Thymosin Beta-4: A Novel Treatment for Acanthamoeba Keratitis

Author

Victoria A. Murphey, Clemson UniversityFollow

Date of Award

5-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Committee Chair/Advisor

Dr. Lesly Temesvari

Committee Member

Dr. James Morris

Committee Member

Dr. Zhicheng Dou

Abstract

Acanthamoeba keratitis (AK) is a severe corneal infection caused by the free-living amoeba, Acanthamoeba. Both stages of its life cycle (trophozoite and cyst) cause infection, primarily in contact lens wearers. It is often misdiagnosed, leading to delayed treatment and poor clinical outcomes. Current treatment options for AK rely on anti-amoebic agents that are toxic to corneal epithelial cells. Further, no single drug can eliminate both forms of the amoeba. Approximately 30% of all AK infections require a corneal transplant.

Thymosin beta-4 (Tβ4) is a G-actin binding protein synthesized in almost all human cells, including corneal epithelial cells. Tβ4 exhibits wound-healing and anti-inflammatory properties in the cornea. It has demonstrated efficacy in clinical trials as a topical treatment for corneal diseases, such as dry eye syndrome and neurotrophic keratopathy. This study assessed the potential of Tβ4 as a treatment for AK by evaluating its effects on Acanthamoeba-induced cytotoxicity in human corneal epithelial cells (HCE-S) and its impact on amebic stage conversion.

We observed that Tβ4 improved HCE-S cell viability in serum-free media when exposed to Acanthamoeba. This protection was not the result of increased proliferation of HCE-S cells nor the direct killing of Acanthamoeba trophozoites. Notably, Tβ4 did not protect HCE-S cells from Acanthamoeba-induced cytotoxicity in serum-supplemented media, suggesting that serum components may influence or mask Tβ4’s activity.

We also determined that Tβ4 inhibits encystation, but not excystation. We found that Tβ4 altered actin localization in trophozoites early in encystation. Overall, Tβ4 represents a potential non-toxic therapy for AK that warrants further investigation.

Recommended Citation

Murphey, Victoria A., "Thymosin Beta-4: A Novel Treatment for Acanthamoeba Keratitis" (2025). All Theses. 4507.
https://open.clemson.edu/all_theses/4507

Author ORCID Identifier

https://orcid.org/0000-0002-6089-7222