Toxicity evaluation of antiglaucoma drugs using stratified human cultivated corneal epithelial sheets

• Published in: Investigative ophthalmology & visual science Vol. 53; no. 9; pp. 5154 - 5160
• Main Authors: Nakagawa, Suguru, Usui, Tomohiko, Yokoo, Seiichi, Omichi, Sachiko, Kimakura, Mikiko, Mori, Yosai, Miyata, Kazunori, Aihara, Makoto, Amano, Shiro, Araie, Makoto
• Format: Journal Article
• Language: English
• Published: United States 03.08.2012
• Subjects: Antihypertensive Agents - toxicity; Benzalkonium Compounds - toxicity; Cell Membrane Permeability; Cell Survival; Cells, Cultured; Culture Media, Serum-Free; Drug Combinations; Epithelium, Corneal - drug effects; 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
• ISSN: 1552-5783; 1552-5783
• DOI: 10.1167/iovs.12-9685

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. 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. 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. 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.