The evaluation of cytoxicity of ocular hypotensive therapy to cultured human corneal epithelial cells

Abstract

BACKGROUND: Corneal epithelial defect is a corneal epithelial cells’ (CEpC) disruption of various origin. In patients with corneal epithelial defect, glaucoma is a frequent concomitant disease demanding prescription of hypotensive medications, most of which containing benzalkonium chloride.

AIM: The aim of this study is to evaluate cytotoxicity of antiglaucoma drugs, as well as benzalkonium chloride (BAK), to human CEpC in vitro.

MATERIALS AND METHODS: The study was carried out on primary cultures of human CEpC. Cytotoxicity of dorzolamide, brimonidine, timolol (dilutions 1/100, 1/50, 1/20, 1/10, a 24-hour exposure) and of BAK was estimated on the model of intact epithelium (monolayer). Benzalkonium chloride was evaluated in concentrations equals to its concentration in tested ophthalmic solutions. Cytotoxicity of dorzolamide, brimonidine, timolol (dilutions 1/100, 1/20, a 48-hour exposure) was evaluated on the model of corneal epithelial defect (damage of the monolayer). The medication’s cytotoxicity was estimated by cellular changes (phase-contrast microscopy) and by the MTS-test’s results.

RESULTS: Among BAK-free medications: dorzolamide (1/50, 1/20, 1/10 dilutions), brimonidine (1/10 dilution) — induce CEpCs’ pathological changes, whereas timolol (all tested dilutions) is non-toxic. BAK-preserved drugs: dorzolamide, brimonidine, timolol (1/100, 1/50, 1/20, 1/10 dilutions) — induce CEpCs’ damage, their viability reduction, and corneal epithelial defect closure inhibition. BAK shows similar effect in tested concentrations.

CONCLUSIONS: Cytotoxicity of antiglaucoma drugs is attributed to their component — benzalkonium chloride. Administration of preserved drugs is not reasonable in eyes with corneal epithelial defect of various origin.

Keywords

dorzolamide / brimonidine / timolol / benzalkonium chloride / corneal epithelial cells / cytotoxicity / epithelial defect

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