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Invest Ophthalmol Vis Sci ; 53(9): 5154-60, 2012 Aug 03.
Article in English | MEDLINE | ID: mdl-22695966

ABSTRACT

PURPOSE: To investigate the toxicity profiles of seven antiglaucoma topical eye drops and benzalkonium chloride (BAC) using stratified cultivated human corneal epithelial cell sheets (HCES) in a serum-free culture system. METHODS: A range of prostaglandin analogies and preservatives, including BAC, sofZia (SZ), sodium benzoate (SB), and polyquaternium-1 (PQ) were tested. The barrier function and cell viability were examined by a carboxyfluorescein permeability assay and WST-1 assay. Histological evaluation of the HCES was also performed after application of each solution. RESULTS: The carboxyfluorescein permeability assay had a higher sensitivity for the detection of toxicity of test solutions than the WST-1 assay or histological examination. Latanoprost BAC, latanoprost/timolol BAC, and 0.02% or higher concentration of BAC were the most toxic, followed by latanoprost SB, latanoprost preservative-free, BAC 0.002%, and travoprost/ latanoprost PQ. Travoprost SZ and tafluprost BAC (preserved with 0.001% BAC) was the least toxic in our experimental conditions. CONCLUSIONS: The carboxyfluorescein permeability assay using HCES in a serum-free system was the most useful for the quantification of toxicity of ophthalmic solutions. Among the regimens examined, a BAC concentration of 0.001% or lower or non-BAC preservative sofZia was suggested to be the least toxic to the ocular surface.


Subject(s)
Antihypertensive Agents/toxicity , Epithelium, Corneal/drug effects , Benzalkonium Compounds/toxicity , Cell Membrane Permeability , Cell Survival , Cells, Cultured , Culture Media, Serum-Free , Drug Combinations , Fluoresceins/metabolism , Fluorescent Dyes/metabolism , Glaucoma/drug therapy , Humans , Membrane Proteins/metabolism , Ophthalmic Solutions/toxicity , Phosphoproteins/metabolism , Preservatives, Pharmaceutical/toxicity , Prostaglandins F, Synthetic/toxicity , Timolol/toxicity , Zonula Occludens-1 Protein
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