PMID- 22695966 OWN - NLM STAT- MEDLINE DCOM- 20121106 LR - 20131121 IS - 1552-5783 (Electronic) IS - 0146-0404 (Linking) VI - 53 IP - 9 DP - 2012 Aug 3 TI - Toxicity evaluation of antiglaucoma drugs using stratified human cultivated corneal epithelial sheets. PG - 5154-60 LID - 10.1167/iovs.12-9685 [doi] AB - 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. FAU - Nakagawa, Suguru AU - Nakagawa S AD - Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan. FAU - Usui, Tomohiko AU - Usui T FAU - Yokoo, Seiichi AU - Yokoo S FAU - Omichi, Sachiko AU - Omichi S FAU - Kimakura, Mikiko AU - Kimakura M FAU - Mori, Yosai AU - Mori Y FAU - Miyata, Kazunori AU - Miyata K FAU - Aihara, Makoto AU - Aihara M FAU - Amano, Shiro AU - Amano S FAU - Araie, Makoto AU - Araie M LA - eng PT - Journal Article DEP - 20120803 PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Antihypertensive Agents) RN - 0 (Benzalkonium Compounds) RN - 0 (Culture Media, Serum-Free) RN - 0 (Drug Combinations) RN - 0 (Fluoresceins) RN - 0 (Fluorescent Dyes) RN - 0 (Membrane Proteins) RN - 0 (Ophthalmic Solutions) RN - 0 (Phosphoproteins) RN - 0 (Preservatives, Pharmaceutical) RN - 0 (Prostaglandins F, Synthetic) RN - 0 (TJP1 protein, human) RN - 0 (Zonula Occludens-1 Protein) RN - 3301-79-9 (6-carboxyfluorescein) RN - 817W3C6175 (Timolol) SB - IM MH - Antihypertensive Agents/*toxicity MH - Benzalkonium Compounds/toxicity MH - Cell Membrane Permeability MH - Cell Survival MH - Cells, Cultured MH - Culture Media, Serum-Free MH - Drug Combinations MH - Epithelium, Corneal/*drug effects MH - Fluoresceins/metabolism MH - Fluorescent Dyes/metabolism MH - Glaucoma/drug therapy MH - Humans MH - Membrane Proteins/metabolism MH - Ophthalmic Solutions/toxicity MH - Phosphoproteins/metabolism MH - Preservatives, Pharmaceutical/toxicity MH - Prostaglandins F, Synthetic/toxicity MH - Timolol/toxicity MH - Zonula Occludens-1 Protein EDAT- 2012/06/15 06:00 MHDA- 2012/11/07 06:00 CRDT- 2012/06/15 06:00 PHST- 2012/06/15 06:00 [entrez] PHST- 2012/06/15 06:00 [pubmed] PHST- 2012/11/07 06:00 [medline] AID - iovs.12-9685 [pii] AID - 10.1167/iovs.12-9685 [doi] PST - epublish SO - Invest Ophthalmol Vis Sci. 2012 Aug 3;53(9):5154-60. doi: 10.1167/iovs.12-9685.