Evaluation of Acute Corneal Barrier Change Induced by Topically Applied Preservatives Using Corneal Transepithelial Electric Resistance In Vivo

Kusano, Mao; Uematsu, Masafumi; Kumagami, Takeshi; Sasaki, Hidetada; Kitaoka, Takashi

doi:10.1097/ico.0b013e3181a3c3e6

Cited by 48 publications

(61 citation statements)

References 42 publications

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“…33 By using this method, we determined that the TER of the cornea of normal live rabbits was 701.6  43.1 ·cm 2 , which is considered to be an adequate value when compared to previous reports that have measured the corneal TER. 18,19,[28][29][30] After exposure to travoprost Z, which uses sofZia as the preservative system, TER exhibited almost the same results as those of the negative control, HBSS. This suggests that travoprost Z does not cause acute corneal barrier dysfunction.…”

Section: Discussionsupporting

confidence: 51%

“…18 This novel approach for examining the clinical instillation of eyedrops has revealed that exposure to BAC concentrations between 0.005%-0.02% immediately causes acute corneal dysfunction. 19,20 In our preliminary experiments, we found that travoprost caused low acute corneal impairment regardless of whether it contained 0.015% BAC. Therefore, we decided to further examine this phenomenon by electrophysiologically comparing the acute corneal barrier dysfunction induced by travoprost Z, travoprost, and 0.015%…”

Section: Introductionmentioning

confidence: 99%

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Polyoxyethylene Hydrogenated Castor Oil Modulates Benzalkonium Chloride Toxicity: Comparison of Acute Corneal Barrier Dysfunction Induced by Travoprost Z and Travoprost

Uematsu

Kumagami

Shimoda

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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Methods: Corneal transepithelial electrical resistance (TER) was measured in live white Japanese rabbits by two Ag/AgCl electrodes placed in the anterior aqueous chamber and on the cornea. We evaluated corneal TER changes after a 60-s exposure to travoprost Z, travoprost, and 0.015% BAC.Similarly, TER changes were evaluated after corneas were exposed for 60 s to the travoprost additives EDTA, boric acid, mannitol, trometamol, and polyoxyethylene hydrogenated castor oil 40 (HCO-40) with or without BAC. Corneal damage was examined after exposure to BAC with or without travoprost additives using scanning electron microscopy (SEM) and a cytotoxicity assay.Results: Although no decreases of TER were noted after exposure to travoprost Z with sofZia and travoprost with 0.015% BAC, a significant decrease of corneal TER was observed after 0.015% BAC exposure. With the exception of for BAC, no corneal TER decreases were observed for any travoprost additives. After corneal exposure to travoprost additives with BAC, HCO-40 was able to prevent the BAC-induced TER decrease. SEM observations and the cytotoxicity assay confirmed that there was a remarkable improvement of BAC-induced corneal epithelial toxicity after addition of HCO-40 to the BAC.

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Polyoxyethylene Hydrogenated Castor Oil Modulates Benzalkonium Chloride Toxicity: Comparison of Acute Corneal Barrier Dysfunction Induced by Travoprost Z and Travoprost

Uematsu

Kumagami

Shimoda

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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“…In our formerly established method, we also demonstrated that one minute exposure to 0.02% BAC immediately caused acute corneal TER decrease to 20-30% (Kusano et al, 2010: Onizuka et al, 2014.…”

Section: Discussionmentioning

confidence: 94%

“…In order to overcome that problem, in this study we recently developed a less invasive corneal TER measurement method. In previous studies, we demonstrated that benzalkonium chloride (BAC) concentrations between 0.005% and 0.02% immediately caused acute corneal barrier dysfunction (Kusano et al, 2010: Uematsu et al, 2007. So, our aim in this study is to evaluate acute corneal permeability change after instillation of BAC using a newly developed in vivo less invasive corneal TER measurement method in rabbits.…”

Section: Discussionmentioning

confidence: 99%

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A novel in vivo corneal trans-epithelial electrical resistance measurement device

Uematsu

Mohamed

Onizuka

et al. 2015

Journal of Pharmacological and Toxicological Methods

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Purpose: To develop a device that is capable of easily measuring corneal transepithelial electrical resistance (TER) and changes in the corneal barrier function. Methods:We had previously developed an in vivo method for measuring corneal TER using intraocular electrode. This method can be used to precisely measure the decline of the corneal barrier function after instillation of benzalkonium chloride (BAC). In order to lessen the invasiveness of that procedure, we further refined the method for measuring the corneal TER by developing electrodes that could be placed on the cornea and in the conjunctival sac instead of inserting them into the anterior chamber. TER was then calculated by subtracting the electrical resistance, which lacked the corneal epithelial input, from the whole electrical resistance that was measured between the electrodes. Slit lamp examination and scanning electron microscopy (SEM) were used to determine safety of the new device. Corneal TER changes after exposure to 0.02% BAC were determined using the new device as well as SEM and transmission electron microscopy (TEM).Results: Slit lamp examination before and after exposure of rabbits' corneas to the sensor confirmed safety of the device. SEM examination revealed no difference of the corneal epithelium which exposed to the new device with normal corneas. SEM and 3 TEM pictures revealed damaged microvilli and tight junctions after instillation of 0.02% BAC. TER change after treatment with 0.02%BAC was similar to those determined by the established anterior chamber method. Conclusion:We succeeded to develop a less invasive device for corneal TER measurement in vivo in animals. This new device may be applicable in the future for clinical use in humans.

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Flexible probe for in vivo quantification of corneal epithelium permeability through non-invasive tetrapolar impedance measurements

Guimerà‐Brunet

Illa

Traver

et al. 2013

Biomed Microdevices

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Studies concerning the functional status of the corneal epithelium are of special interest due to its key role in preventing ocular surface disease and corneal infections. In particular, quantitative measurements of the epithelium permeability translayer electrical resistance (TER) have been proven as a sensitive in vitro test for evaluation of the corneal barrier function. In a recent work from the authors (Guimera et al. Biosens. Bioelectron. 31:55-61, 2012), a novel method to non-invasively assess the corneal epithelial permeability by using tetrapolar impedance measurements, based on the same TER theoretical principles, was presented and validated using a rigid sensing device. In this work, the usability of this method has been dramatically improved by using SU-8 photoresist as a substrate material. The flexibility of this novel sensing device makes no need to apply pressure on the cornea to ensure the electrical contact between the electrodes and the corneal surface. The feasibility of this flexible sensor has been evaluated in vivo by increasing the permeability of rabbit corneal epithelium. For that, different concentrations of benzalkonium chloride (BAC) solution were instilled on different rabbit corneas. The obtained results have been compared with measurements of the permeability to sodium fluorescein of different excised corneas, a well-known method used to evaluate the corneal barrier function, to demonstrate the feasibility of this novel flexible sensor for quantifying the corneal epithelium permeability in vivo in a non-invasive way.

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Evaluation of Acute Corneal Barrier Change Induced by Topically Applied Preservatives Using Corneal Transepithelial Electric Resistance In Vivo

Abstract: Instillation with BAC immediately disrupted the corneal epithelium. Corneal epithelial cell death is supposed to be associated with a decline in barrier function; thus, corneal TER measurement in vivo can assess the acute toxicity of preservatives added to ophthalmic drugs.

Cited by 48 publications

References 42 publications

Polyoxyethylene Hydrogenated Castor Oil Modulates Benzalkonium Chloride Toxicity: Comparison of Acute Corneal Barrier Dysfunction Induced by Travoprost Z and Travoprost

Polyoxyethylene Hydrogenated Castor Oil Modulates Benzalkonium Chloride Toxicity: Comparison of Acute Corneal Barrier Dysfunction Induced by Travoprost Z and Travoprost

A novel in vivo corneal trans-epithelial electrical resistance measurement device

Flexible probe for in vivo quantification of corneal epithelium permeability through non-invasive tetrapolar impedance measurements

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