Recombinant Human Thymosin β4 (rhTβ4) Modulates the Anti-Inflammatory Responses to Alleviate Benzalkonium Chloride (BAC)-Induced Dry Eye Disease

Int J Mol Sci. 2022 May 13;23(10):5458. doi: 10.3390/ijms23105458.

Abstract

Dry eye disease (DED) is a multifactorial ocular disorder that interferes with daily living and reduces quality of life. However, there is no most ideal therapeutic treatment to address all the deleterious defects of DED. The purpose of this study was to investigate the ability of recombinant human thymosin β4 (rhTβ4) to promote healing in a benzalkonium chloride (BAC)-induced mice DED model and the anti-inflammatory effects involved in that process. Eye drops consisting of 0.05% and 0.1% rhTβ4 were used for treatment of DED. Tear volume and corneal staining scores were measured after 7 days. Periodic acid-Schiff staining for gobleT cells in conjunctiva, immunohistochemical staining for CD4+ T cells, TUNEL assay for apoptotic positive cells in cornea and conjunctiva, qRT-PCR and ELISA assays for multiple cytokines were performed. All clinical parameters showed improvement in both the 0.05% and 0.1% rhTβ4 groups. Specifically, topical application of rhTβ4 significantly increased conjunctival gobleT cells and reduced apoptotic cells in conjunctiva. Mechanically, the rhTβ4 groups showed significantly reduced inflammatory cytokine levels and CD4+ T cells in conjunctiva by blocking NF-κB (nuclear factor kappa B) activation, suggesting that 0.05-0.1% rhTβ4 eye drops may be used as a potential therapeutic treatment for DED.

Keywords: benzalkonium chloride (BAC); dry eye disease (DED); inflammation; recombinant human thymosin β4 (rhTβ4).

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Benzalkonium Compounds* / pharmacology
  • Cytokines / therapeutic use
  • Disease Models, Animal
  • Dry Eye Syndromes* / chemically induced
  • Dry Eye Syndromes* / drug therapy
  • Humans
  • Mice
  • NF-kappa B
  • Ophthalmic Solutions / adverse effects
  • Quality of Life
  • Thymosin

Substances

  • Anti-Inflammatory Agents
  • Benzalkonium Compounds
  • Cytokines
  • NF-kappa B
  • Ophthalmic Solutions
  • thymosin beta(4)
  • Thymosin

Grants and funding

This research received no external funding.