Multiple Endpoint Analysis of the 3D-Reconstituted Corneal Epithelium after Treatment with Benzalkonium Chloride: Early Detection of Toxic Damage

Pauly, Aude; Méloni, Marisa; Brignole-Baudouin, Françoise; Warnet, Jean‐Michel; Baudouin, Christophe

doi:10.1167/iovs.08-2992

Cited by 114 publications

(83 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lymphocytes seem to be very sensitive to the cytotoxic effect of BAK. Cytotoxic and proapoptotic BAK concentrations for corneal and conjunctiva cells are higher than seen in this study for lymphocytes, and vary between 0.0001 and 0.02%, but most of them are close to the latter figure [5,7,8,14,17,18]. Huge differences in these concentrations are probably due to differences in methods of cell treatments by BAK (especially in treatment and recovery time) and sensitivities of assays.…”

Section: Discussion Discussion Discussion Discussionmentioning

confidence: 58%

“…Although lymphocytes do not infiltrate the cornea in physiological conditions, they are present in other parts of the anterior segment of the eye as an anterior chamber or a conjunctiva in both physiological and pathological conditions and are a subject for BAK stimulation. Moreover, exposure to BAK increases permability of eye tissues [4,5] www.fhc.viamedica.pl adhesion molecules helping lymphocytes to reach the site of inflammation, and also expression of HLA-DR, which is crucial for antigen presentation needed for lymphocyte activation [1,7]. This data is supported by clinical observations showing an immunologic reaction with increased presence of lymphocytes, Langerhans cells and macrophages in patients subjected to chronic application of preservatives.…”

Section: Discussion Discussion Discussion Discussionmentioning

confidence: 95%

“…Diagrams were prepared using GraphPad Prism software. Significant differences (p < 0.05) to the control are marked as * [5]. Proliferation of human corneal keratocytes has also been measured by [ 3 H] thymidine methodology.…”

Section: Discussion Discussion Discussion Discussionmentioning

confidence: 99%

“…It also causes protein denaturation and disruption of the cytoplasmatic membranes [1]. This phenomenon could be helpful in increasing the penetrative abilities of the ophthalmologic solution's active compounds [4,5]. Moreover, some of the active ophthalmological compounds e.g.…”

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

See 3 more Smart Citations

Benzalkonium chloride (BAK) induces apoptosis or necrosis, but has no major influence on the cell cycle of Jurkat cells

Pożarowska¹,

Pożarowski²

2011

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Section: Discussion Discussion Discussion Discussionmentioning

confidence: 58%

Section: Discussion Discussion Discussion Discussionmentioning

confidence: 95%

Section: Discussion Discussion Discussion Discussionmentioning

confidence: 99%

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

See 2 more Smart Citations

Benzalkonium chloride (BAK) induces apoptosis or necrosis, but has no major influence on the cell cycle of Jurkat cells

Pożarowska¹,

Pożarowski²

2011

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

“…The MTT solution could penetrate only two or three layers from the basal side because this solution was placed under the basal side of the models. This procedure may underestimate the mild irritancy that has toxic effects only in the superficial layer of the corneal epithelium (Pauly et al ., 2009). To overcome this issue, different indicators such as occludin, interleukin‐8 and MUC1 have been proposed (Meloni et al ., 2010; Song and Joo, 2004).…”

Section: Introductionmentioning

confidence: 99%

Predictive performance of the Vitrigel‐eye irritancy test method using 118 chemicals

Yamaguchi

Kojima²,

Takezawa

2015

J of Applied Toxicology

View full text Add to dashboard Cite

We recently developed a novel Vitrigel‐eye irritancy test (EIT) method. The Vitrigel‐EIT method is composed of two parts, i.e., the construction of a human corneal epithelium (HCE) model in a collagen vitrigel membrane chamber and the prediction of eye irritancy by analyzing the time‐dependent profile of transepithelial electrical resistance values for 3 min after exposing a chemical to the HCE model. In this study, we estimated the predictive performance of Vitrigel‐EIT method by testing a total of 118 chemicals. The category determined by the Vitrigel‐EIT method in comparison to the globally harmonized system classification revealed that the sensitivity, specificity and accuracy were 90.1%, 65.9% and 80.5%, respectively. Here, five of seven false‐negative chemicals were acidic chemicals inducing the irregular rising of transepithelial electrical resistance values. In case of eliminating the test chemical solutions showing pH 5 or lower, the sensitivity, specificity and accuracy were improved to 96.8%, 67.4% and 84.4%, respectively. Meanwhile, nine of 16 false‐positive chemicals were classified irritant by the US Environmental Protection Agency. In addition, the disappearance of ZO‐1, a tight junction‐associated protein and MUC1, a cell membrane‐spanning mucin was immunohistologically confirmed in the HCE models after exposing not only eye irritant chemicals but also false‐positive chemicals, suggesting that such false‐positive chemicals have an eye irritant potential. These data demonstrated that the Vitrigel‐EIT method could provide excellent predictive performance to judge the widespread eye irritancy, including very mild irritant chemicals. We hope that the Vitrigel‐EIT method contributes to the development of safe commodity chemicals. Copyright © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.

show abstract

An overview of current alternative models in the context of ocular surface toxicity

Bonneau

Baudouin

Goazigo

et al. 2021

J of Applied Toxicology

Self Cite

View full text Add to dashboard Cite

The 21st century has seen a steadily increasing social awareness of animal suffering, with increased attention to ethical considerations. Developing new integrated approaches to testing and assessment (IATA) strategies is an Organisation for Economic Co‐operation and Development (OECD) goal to reduce animal testing. Currently, there is a lack of alternative models to test for ocular surface toxicity (aside from irritation) in lieu of the Draize eye irritation test (OECD guideline No. 405) performed in rabbits. Five alternative in vitro or ex vivo methods have been validated to replace this reference test, but only in combination. However, pathologies like Toxicity‐Induced Dry Eye (TIDE), cataract, glaucoma, and neuropathic pain can occur after exposure to a pharmaceutical product or chemical and therefore need to be anticipated. To do so, new models of lacrimal glands, lens, and neurons innervating epithelia are required. These models must take into account real‐life exposure (dose, time, and tear film clearance). The scientific community is working hard to develop new, robust, alternative, in silico, and in vitro models, while attempting to balance ethics and availability of biological materials. This review provides a broad overview of the validated methods for analyzing ocular irritation and those still used by some industries, as well as promising models that need to be optimized according to the OECD. Finally, we give an overview of recently developed innovative models, which could become new tools in the evaluation of ocular surface toxicity within the scope of IATAs.

show abstract

Multiple Endpoint Analysis of the 3D-Reconstituted Corneal Epithelium after Treatment with Benzalkonium Chloride: Early Detection of Toxic Damage

Cited by 114 publications

References 49 publications

Benzalkonium chloride (BAK) induces apoptosis or necrosis, but has no major influence on the cell cycle of Jurkat cells

Benzalkonium chloride (BAK) induces apoptosis or necrosis, but has no major influence on the cell cycle of Jurkat cells

Predictive performance of the Vitrigel‐eye irritancy test method using 118 chemicals

An overview of current alternative models in the context of ocular surface toxicity

Contact Info

Product

Resources

About