Acute Corneal Epithelial Change after Instillation of Benzalkonium Chloride Evaluated Using a Newly Developed in vivo Corneal Transepithelial Electric Resistance Measurement Method

Uematsu, Masafumi; Kumagami, Takeshi; Kusano, Mao; Yamada, Koki; Mishima, Kentaro; Fujimura, Koichi; Sasaki, Hidetada; Kitaoka, Takashi

doi:10.1159/000109986

Cited by 55 publications

(65 citation statements)

References 46 publications

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“…In addition, TER was monitored with a recorder, which shows TER changes continuously. To our knowledge, no other study has evaluated acute corneal change within few second in vivo (Uematsu et al, 2007). However, the invasiveness of that procedure by inserting one electrode inside the anterior chamber makes it impossible for being used in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…That design more accurately reflects the clinical instillation of ophthalmic drugs and gives us a relevant data about the acute corneal toxicity of some eye drops (Kusano et al, 2010: Onizuka et al, 2014: Uematsu et al, 2007). …”

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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Section: Discussionmentioning

confidence: 99%

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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“…Test methods in vivo , ex vivo and in vitro have been developed to predict eye irritation (Yamaguchi et al ., 2013). Concerning eye irritation tests (EITs) in vivo , the Draize rabbit EIT has been mainly utilized for evaluating cosmetic ingredients (Draize et al ., 1944; OECD, 2012a) and pharmaceutical agents (Uematsu et al ., 2007). Regarding those ex vivo , excised bovine corneas and chicken eyes successfully contributed to the establishment of Organisation for Economic Co‐operation and Development (OECD) Test Guidelines as the bovine corneal opacity permeability test (OECD, 2013) and isolated chicken eye test (OECD, 2009), respectively.…”

Section: Introductionmentioning

confidence: 99%

“…Here, the scaffold was fabricated on a polyethylene terephthalate (PET) membrane of a Millicell chamber appropriate for the transepithelial electrical resistance (TEER) assay of epithelial cells. TEER is known as a suitable method for evaluating the integrity of the tight junction of corneal epithelium in vivo (Uematsu et al ., 2007). We examined four chemicals using the HCE model, and consequently demonstrated that the time‐dependent relative changes of TEER are useful indicators to assess ocular irritancy effects of chemicals even in the middle category (Takezawa et al ., 2011a).…”

Section: Introductionmentioning

confidence: 99%

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

Yamaguchi

Kojima²,

Takezawa

2015

J of Applied Toxicology

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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.

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Current perspectives on corneal collagen crosslinking (CXL)

Subasinghe

Ogbuehi

Dias

2018

Graefes Arch Clin Exp Ophthalmol

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Corneal collagen crosslinking has revolutionized the treatment of keratoconus and post-refractive corneal ectasia in the past decade. Corneal crosslinking with riboflavin and ultraviolet A is proposed to halt the progression of keratectasia. In the original "Conventional Dresden Protocol" (C-CXL), the epithelium is removed prior to the crosslinking process to facilitate better absorption of riboflavin into the corneal stroma. Studies analyzing its short- and long-term outcomes revealed that although there are inconsistencies as to the effectiveness of this technique, the advantages prevail over the disadvantages. Therefore, corneal crosslinking (CXL) is widely used in current practice to treat keratoconus. In an attempt to improve the visual and topographical outcomes of C-CXL and to minimize time-related discomfort and endothelial-related side effects, various modifications such as accelerated crosslinking and transepithelial crosslinking methods have been introduced. The comparison of outcomes of these modified techniques with C-CXL has also returned contradictory results. Hence, it is difficult to clearly identify an optimal procedure that can overcome issues associated with the CXL. This review provides an up-to-date analysis on clinical and laboratory findings of these popular crosslinking protocols used in the treatment of keratoconus. It is evident from this review that in general, these modified techniques have succeeded in minimizing the immediate complications of the C-CXL technique. However, there were contradictory viewpoints regarding their effectiveness when compared with the conventional technique. Therefore, these modified techniques need to be further investigated to arrive at an optimal treatment option for keratoconus.

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Acute Corneal Epithelial Change after Instillation of Benzalkonium Chloride Evaluated Using a Newly Developed in vivo Corneal Transepithelial Electric Resistance Measurement Method

Cited by 55 publications

References 46 publications

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

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

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

Current perspectives on corneal collagen crosslinking (CXL)

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