Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells

Masahiko Ayaki1, Atsuo Iwasawa2, Yoichi Inoue31Department of Ophthalmology, Saitama National Hospital, Wako, Japan; 2Life Particle Interaction Engineering Creation, New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan; 3Department of Ophthalmology, Olympia Eye Hospital, Tokyo, Jap...

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Autores principales: Masahiko Ayaki, Atsuo Iwasawa, Yoichi Inoue
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Publicado: Dove Medical Press 2010
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spelling oai:doaj.org-article:f15638284e574c5aad17574944148cd42021-12-02T02:44:38ZToxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells1177-54671177-5483https://doaj.org/article/f15638284e574c5aad17574944148cd42010-10-01T00:00:00Zhttp://www.dovepress.com/toxicity-of-antiglaucoma-drugs-with-and-without-benzalkonium-chloride--a5516https://doaj.org/toc/1177-5467https://doaj.org/toc/1177-5483Masahiko Ayaki1, Atsuo Iwasawa2, Yoichi Inoue31Department of Ophthalmology, Saitama National Hospital, Wako, Japan; 2Life Particle Interaction Engineering Creation, New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan; 3Department of Ophthalmology, Olympia Eye Hospital, Tokyo, JapanPurpose: The toxicity of antiglaucoma medications to ocular surface cells has been evaluated extensively; however, the toxicity to corneal endothelial cells (CECs) remains elusive. Our aim is to evaluate the toxicity of antiglaucoma medications to CECs using an in vitro toxicity assay.Methods: Primary cultures of human (H) CECs derived from eye bank specimens were established. Following exposure of HCECs to test solutions for 10, 30, or 60 minutes, or 48 hours, we measured cell viability using a WST-1 assay. Test solutions were diluted in culture media and included 0.5% Timoptol®, preservative-free 0.5% timolol maleate, 1% Trusopt®, preservative-free 1% dorzolamide, Travatan®, Travatan Z®, Xalatan®, and benzalkonium chloride (BAK). To assess cell viability, the value of the test culture well after treatment was expressed as a percentage of that of the control well. Toxicity of each solution was compared using the cell viability score (CVS).Results: After exposure to 10-fold dilutions of test solutions for 48 hours, HCEC viabilities were 48.5% for 0.5% Timoptol, 80.9% for preservative-free 0.5% timolol maleate, 47.0% for 1% Trusopt, 71.7% for preservative-free 1% dorzolamide, 55.5% for Travatan, 88.5% for Travatan Z, and 52.5% for Xalatan. Exposure to test solutions diluted 100-fold or more resulted in HCEC viabilities > 80%, with the exception of preservative-free 1% dorzolamide, which resulted in a viability of 72.0% at a dilution of 100-fold. Based on CVS, the order of cell viability was Travatan Z ≥ preservative-free timolol maleate = preservative-free dorzolamide > 0.5% Timoptol = 1% Trusopt > Travatan ≥ Xalatan. Assessment of the combined effect of drug and BAK revealed that latanoprost reduced the toxicity of BAK.Conclusion: Antiglaucoma eye drops produced HCEC toxicity that appeared to depend on the presence of BAK. Because dilution of the antiglaucoma solutions resulted in markedly lower HCEC toxicity, HCEC damage due to antiglaucoma medication may occur only in rare cases. The CVS was useful for comparison of the toxicity of the drugs.Keywords: cell viability score, eye drop, preservatives Masahiko AyakiAtsuo IwasawaYoichi InoueDove Medical PressarticleOphthalmologyRE1-994ENClinical Ophthalmology, Vol 2010, Iss default, Pp 1217-1222 (2010)
institution DOAJ
collection DOAJ
language EN
topic Ophthalmology
RE1-994
spellingShingle Ophthalmology
RE1-994
Masahiko Ayaki
Atsuo Iwasawa
Yoichi Inoue
Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells
description Masahiko Ayaki1, Atsuo Iwasawa2, Yoichi Inoue31Department of Ophthalmology, Saitama National Hospital, Wako, Japan; 2Life Particle Interaction Engineering Creation, New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan; 3Department of Ophthalmology, Olympia Eye Hospital, Tokyo, JapanPurpose: The toxicity of antiglaucoma medications to ocular surface cells has been evaluated extensively; however, the toxicity to corneal endothelial cells (CECs) remains elusive. Our aim is to evaluate the toxicity of antiglaucoma medications to CECs using an in vitro toxicity assay.Methods: Primary cultures of human (H) CECs derived from eye bank specimens were established. Following exposure of HCECs to test solutions for 10, 30, or 60 minutes, or 48 hours, we measured cell viability using a WST-1 assay. Test solutions were diluted in culture media and included 0.5% Timoptol®, preservative-free 0.5% timolol maleate, 1% Trusopt®, preservative-free 1% dorzolamide, Travatan®, Travatan Z®, Xalatan®, and benzalkonium chloride (BAK). To assess cell viability, the value of the test culture well after treatment was expressed as a percentage of that of the control well. Toxicity of each solution was compared using the cell viability score (CVS).Results: After exposure to 10-fold dilutions of test solutions for 48 hours, HCEC viabilities were 48.5% for 0.5% Timoptol, 80.9% for preservative-free 0.5% timolol maleate, 47.0% for 1% Trusopt, 71.7% for preservative-free 1% dorzolamide, 55.5% for Travatan, 88.5% for Travatan Z, and 52.5% for Xalatan. Exposure to test solutions diluted 100-fold or more resulted in HCEC viabilities > 80%, with the exception of preservative-free 1% dorzolamide, which resulted in a viability of 72.0% at a dilution of 100-fold. Based on CVS, the order of cell viability was Travatan Z ≥ preservative-free timolol maleate = preservative-free dorzolamide > 0.5% Timoptol = 1% Trusopt > Travatan ≥ Xalatan. Assessment of the combined effect of drug and BAK revealed that latanoprost reduced the toxicity of BAK.Conclusion: Antiglaucoma eye drops produced HCEC toxicity that appeared to depend on the presence of BAK. Because dilution of the antiglaucoma solutions resulted in markedly lower HCEC toxicity, HCEC damage due to antiglaucoma medication may occur only in rare cases. The CVS was useful for comparison of the toxicity of the drugs.Keywords: cell viability score, eye drop, preservatives
format article
author Masahiko Ayaki
Atsuo Iwasawa
Yoichi Inoue
author_facet Masahiko Ayaki
Atsuo Iwasawa
Yoichi Inoue
author_sort Masahiko Ayaki
title Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells
title_short Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells
title_full Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells
title_fullStr Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells
title_full_unstemmed Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells
title_sort toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells
publisher Dove Medical Press
publishDate 2010
url https://doaj.org/article/f15638284e574c5aad17574944148cd4
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AT yoichiinoue toxicityofantiglaucomadrugswithandwithoutbenzalkoniumchloridetoculturedhumancornealendothelialcells
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