Evaluation of the anti-Acanthamoeba activity of two commercial eye drops commonly used to lower eye pressure

Exp Parasitol. 2017 Dec:183:117-123. doi: 10.1016/j.exppara.2017.07.012. Epub 2017 Aug 1.

Abstract

Efficient treatments against Acanthamoeba Keratitis (AK), remains until the moment, as an issue to be solved due to the existence of a cyst stage which is highly resistant to most chemical and physical agents. In this study, two antiglaucoma eye drops were tested for their activity against Acanthamoeba. Moreover, this study was based on previous data which gave us evidence of a possible link between the absences of Acanthamoeba at the ocular surface in patients treated with beta blockers for high eye pressure both containing timolol as active principle. The amoebicidal activity of the tested eye drops was evaluated against four strains of Acanthamoeba using Alamar blue method. For the most active drug the cysticidal activity against A. castellanii Neff cysts and further experiments studying changes in chromatin condensation levels, in the permeability of the plasmatic membrane, the mitochondrial membrane potential and the ATP levels in the treated amoebic strains were done. Even though both eye drops were active against the different tested strains of Acanthamoeba, statistical analysis revealed that one of them (Timolol Sandoz) was the most effective one against all the tested strains presenting IC50s ranging from 0.529% ± 0.206 for the CLC 16 strain to 3.962% ± 0.150 for the type strain Acanthamoeba castellanii Neff. Timolol Sandoz 0.50% seems to induce amoebic cell death by damaging the amoebae at the mitochondrial level. Considering its effect, Timolol Sandoz 0.50% could be used in the case of contact lens wearers and patients with glaucoma.

Keywords: Acanthamoeba; Chemotherapy; Mechanism of action; Mitochondria; Timolol.

MeSH terms

  • Acanthamoeba / drug effects*
  • Acanthamoeba Keratitis / drug therapy
  • Acanthamoeba Keratitis / prevention & control*
  • Adrenergic alpha-2 Receptor Agonists / administration & dosage
  • Adrenergic alpha-2 Receptor Agonists / pharmacology*
  • Adrenergic alpha-2 Receptor Agonists / therapeutic use
  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / pharmacology*
  • Adrenergic beta-Antagonists / therapeutic use
  • Analysis of Variance
  • Apoptosis / drug effects
  • Brimonidine Tartrate / administration & dosage
  • Brimonidine Tartrate / pharmacology
  • Brimonidine Tartrate / therapeutic use
  • Brimonidine Tartrate, Timolol Maleate Drug Combination / administration & dosage
  • Brimonidine Tartrate, Timolol Maleate Drug Combination / pharmacology
  • Brimonidine Tartrate, Timolol Maleate Drug Combination / therapeutic use
  • Glaucoma / drug therapy*
  • Inhibitory Concentration 50
  • Intraocular Pressure / drug effects*
  • Membrane Potential, Mitochondrial / drug effects
  • Ophthalmic Solutions
  • Timolol / administration & dosage
  • Timolol / pharmacology
  • Timolol / therapeutic use

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Adrenergic beta-Antagonists
  • Brimonidine Tartrate, Timolol Maleate Drug Combination
  • Ophthalmic Solutions
  • Brimonidine Tartrate
  • Timolol