Evaluation of the cytotoxic effects of ophthalmic solutions containing benzalkonium chloride on corneal epithelium using an organotypic 3-D model

Khoh‐Reiter, Su; Jessen, Bart

doi:10.1186/1471-2415-9-5

Cited by 37 publications

(19 citation statements)

References 23 publications

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“…In contrast with our results and all literature data on BAC,8 12–19 one recent study did not find any loss of viability when testing BAC alone or BAC-containing latanoprost after a short contact duration from 10 to 60 min using the same model of 3D-corneal epithelium as that used in this study 20. These conflicting results were principally due to the differences in experimental conditions, such as the choice of model or appropriateness of duration of contact.…”

Section: Discussioncontrasting

confidence: 99%

Toxicological evaluation of preservative-containing and preservative-free topical prostaglandin analogues on a three-dimensional-reconstituted corneal epithelium system

Liang

Pauly

Riancho

et al. 2011

British Journal of Ophthalmology

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AimsUsing an established three-dimensional (3D) toxicological model based on reconstituted human corneal epithelium (HCE), this study investigated the tolerability of four topical intraocular-pressure-lowering agents: the commercial solutions of benzalkonium chloride (BAC)-containing 0.005% latanoprost, 0.004% travoprost, 0.03% bimatoprost containing 0.02%, 0.015% and 0.005% BAC, respectively, and the preservative-free (PF) tafluprost. Solutions of 0.01% and 0.02% BAC alone were also evaluated for comparison.MethodsThe 3D-HCEs were treated with solutions for 24 h followed or not by a 24 h recovery period. We used a modified MTT (3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) procedure to assess cell viability in the HCE. Frozen sections of HCE were analysed using fluorescence microscopy for the evaluation of apoptosis (terminal deoxynucleotidyl transferase mediated dUTP nick end labelling), inflammation (ICAM-1) and proliferation (Ki67). Corneal epithelial tight junctions (occludin and tight junction protein 1 (zona occludens 1)) were also assessed by en face confocal microscopy in response to the different eye-drops.ResultsThe MTT test revealed that the cytotoxicity of antiglaucoma eye-drops was primarily related to the concentration of their common BAC preservative (0.02% BAC-latanoprost>0.015% BAC-travoprost>0.005% BAC-bimatoprost). PF-tafluprost did not induce any obvious cytotoxicity, showed the least expression of inflammatory or apoptotic markers and revealed preservation of membrane immunostaining of tight junction proteins in comparison with BAC-containing solutions.ConclusionThe toxicological model of the 3D reconstructed corneal epithelia model confirmed the ocular surface cytotoxicity of BAC-containing antiglaucomatous solutions. Compared with the formulations containing the toxic preservative BAC, PF-tafluprost was well tolerated without inducing significant corneal epithelium deterioration.

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Section: Discussioncontrasting

confidence: 99%

Toxicological evaluation of preservative-containing and preservative-free topical prostaglandin analogues on a three-dimensional-reconstituted corneal epithelium system

Liang

Pauly

Riancho

et al. 2011

British Journal of Ophthalmology

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“…[11][12][13] However, it is impossible to evaluate barrier function using monolayer cells. Although a 3-dimensional stratified corneal epithelial cell model has been established, [14][15][16] this model differs from in vivo human corneal epithelial cells because it uses unnatural immortalized cells. Recently, we have established primary cultivated HCES in a serum-free and antibiotic-free culture system.…”

Section: Discussionmentioning

confidence: 99%

Toxicity of Topical Antifungal Agents to Stratified Human Cultivated Corneal Epithelial Sheets

Kimakura

Usui²,

Yokoo³

et al. 2014

Journal of Ocular Pharmacology and Therapeutics

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“…There has since been much use of the SkinEthic model to investigate the toxicity potential of ophthalmic solutions [39], [42]–[47] including a pre-validation study by Van Goethem et al . in 2006 where the SkinEthic model was shown to be a useful alternative for the in vivo Draize test [15].…”

Section: Discussionmentioning

confidence: 99%

Development of a Curved, Stratified, In Vitro Model to Assess Ocular Biocompatibility

et al. 2014

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PurposeTo further improve in vitro models of the cornea, this study focused on the creation of a three-dimensional, stratified, curved epithelium; and the subsequent characterization and evaluation of its suitability as a model for biocompatibility testing.MethodsImmortalized human corneal epithelial cells were grown to confluency on curved cellulose filters for seven days, and were then differentiated and stratified using an air-liquid interface for seven days before testing. Varying concentrations of a commercial ophthalmic solution containing benzalkonium chloride (BAK), a known cytotoxic agent, and two relevant ocular surfactants were tested on the model. A whole balafilcon A lens soaked in phosphate buffered saline (BA PBS) was also used to assess biocompatibility and verify the validity of the model. Viability assays as well as flow cytometry were performed on the cells to investigate changes in cell death and integrin expression.ResultsThe reconstructed curved corneal epithelium was composed of 3–5 layers of cells. Increasing concentrations of BAK showed dose-dependent decreased cell viability and increased integrin expression and cell death. No significant change in viability was observed in the presence of the surfactants. As expected, the BA PBS combination appeared to be very biocompatible with no adverse change in cell viability or integrin expression.ConclusionsThe stratified, curved, epithelial model proved to be sensitive to distinct changes in cytotoxicity and is suitable for continued assessment for biocompatibility testing of contact lenses. Our results showed that flow cytometry can provide a quantitative measure of the cell response to biomaterials or cytotoxic compounds for both the supernatant and adherent cell populations. As a specifically designed in vitro model of the corneal epithelium, this quantitative model for biocompatibility at the ocular surface may help improve our understanding of cell-material interactions and reduce the use of animal testing.

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Evaluation of the cytotoxic effects of ophthalmic solutions containing benzalkonium chloride on corneal epithelium using an organotypic 3-D model

Cited by 37 publications

References 23 publications

Toxicological evaluation of preservative-containing and preservative-free topical prostaglandin analogues on a three-dimensional-reconstituted corneal epithelium system

Toxicological evaluation of preservative-containing and preservative-free topical prostaglandin analogues on a three-dimensional-reconstituted corneal epithelium system

Toxicity of Topical Antifungal Agents to Stratified Human Cultivated Corneal Epithelial Sheets

Development of a Curved, Stratified, In Vitro Model to Assess Ocular Biocompatibility

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