Identification of cornifelin and early growth response-1 gene as novel biomarkers for in vitro eye irritation using a 3D reconstructed human cornea model MCTT HCE™

Choi, Seunghye; Lee, Miri; Lee, Su Hyon; Jung, Haeng Sun; Kim, Seol Yeong; Chung, Tae Young; Choe, Taeboo; Chun, Young Jin; Lim, Kyung Min

doi:10.1007/s00204-014-1390-8

Cited by 13 publications

(11 citation statements)

References 22 publications

(27 reference statements)

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“…More substances of Category 2 and NI should be evaluated to clearly assess the predictive capacity of this model for the discrimination of Category 2 irritants. In addition, incorporation of secondary markers like IL-8 ( Debbasch et al ., 2005 ), cornifelin expression ( Choi et al ., 2014 ) or occludin expression ( Meloni et al ., 2010 ) along with cell viability measurement may be helpful to enhance predictive capacity of this model for the determination of Category 2 eye irritants although further studies are necessary to confirm it.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCE^TM

Jang

Jung

Yang

et al. 2015

Biomolecules & Therapeutics

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The eye irritation potential of drug candidates or pharmaceutical ingredients should be evaluated if there is a possibility of ocular exposure. Traditionally, the ocular irritation has been evaluated by the rabbit Draize test. However, rabbit eyes are more sensitive to irritants than human eyes, therefore substantial level of false positives are unavoidable. To resolve this species difference, several three-dimensional human corneal epithelial (HCE) models have been developed as alternative eye irritation test methods. Recently, we introduced a new HCE model, MCTT HCETM which is reconstructed with non-transformed human corneal cells from limbal tissues. Here, we examined if MCTT HCETM can be employed to evaluate eye irritation potential of solid substances. Through optimization of washing method and exposure time, treatment time was established as 10 min and washing procedure was set up as 4 times of washing with 10 mL of PBS and shaking in 30 mL of PBS in a beaker. With the established eye irritation test protocol, 11 solid substances (5 non-irritants, 6 irritants) were evaluated which demonstrated an excellent predictive capacity (100% accuracy, 100% specificity and 100% sensitivity). We also compared the performance of our test method with rabbit Draize test results and in vitro cytotoxicity test with 2D human corneal epithelial cell lines.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCE^TM

Jang

Jung

Yang

et al. 2015

Biomolecules & Therapeutics

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“…The MCTT-HCE tissue develops morphology similar to the in vivo human corneal epithelium and expresses corneal-specific markers of differentiation including CK3/ 12, CD44v6, MUC1, and MUC5AC (www.keraskin.co.kr 2020) (Jung et al 2011). The MCTT-HCE cornea model is used as an alternative to animal testing and for the development of ophthalmic therapeutics (Choi et al 2015;Ye et al 2018) (http://biosolutions.co.kr/eng/product/group.asp).…”

Section: In Vitro 3d Corneal Epithelial Model-based Eye Irritation Testsmentioning

confidence: 99%

“…Transcriptomic approaches have been suggested to assist with eye irritation classification. The MCTT HCE tissue model was used to explore new biomarkers during the eye irritation response (Choi et al 2015). MCTT HCE tissues were treated with surfactants, sodium lauryl sulfate (SLS), benzalkonium chloride (BAC), and Triton X-100.…”

Section: Transcriptomic and Proteomic Approachesmentioning

confidence: 99%

In vitro reconstructed 3D corneal tissue models for ocular toxicology and ophthalmic drug development

Kaluzhny

Klausner

2021

In Vitro Cell.Dev.Biol.-Animal

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Testing of all manufactured products and their ingredients for eye irritation is a regulatory requirement. In the last two decades, the development of alternatives to the in vivo Draize eye irritation test method has substantially advanced due to the improvements in primary cell isolation, cell culture techniques, and media, which have led to improved in vitro corneal tissue models and test methods. Most in vitro models for ocular toxicology attempt to reproduce the corneal epithelial tissue which consists of 4-5 layers of non-keratinized corneal epithelial cells that form tight junctions, thereby limiting the penetration of chemicals, xenobiotics, and pharmaceuticals. Also, significant efforts have been directed toward the development of more complex threedimensional (3D) equivalents to study wound healing, drug permeation, and bioavailability. This review focuses on in vitro reconstructed 3D corneal tissue models and their utilization in ocular toxicology as well as their application to pharmacology and ophthalmic research. Current human 3D corneal epithelial cell culture models have replaced in vivo animal eye irritation tests for many applications, and substantial validation efforts are in progress to verify and approve alternative eye irritation tests for widespread use. The validation of drug absorption models and further development of models and test methods for many ophthalmic and ocular disease applications is required.

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“…Especially, the cells which contribute to viability measurement exist in the basal layer of the 3D construct which may underestimate the events occurring at the superficial level (105). To complement the protocol and the predictive capacity of RhCE, biomarkers for eye irritation have been actively studied (106). …”

Section: Current Studies To Advance Eye and Skin Irritation Tests Witmentioning

confidence: 99%

“…Especially, CNFN is reported to increase in barrier-related diseases such as psoriatic skin, atopic dermatitis and mycosis fungoides (107). This suggests that increased expression of CNFN on the exposure to eye irritants might be linked with cellular adaptive responses to augment barrier function through surface cornification and to prevent further permeation of irritants (106). …”

Section: Current Studies To Advance Eye and Skin Irritation Tests Witmentioning

confidence: 99%

Alternatives toIn VivoDraize Rabbit Eye and Skin Irritation Tests with a Focus on 3D Reconstructed Human Cornea-Like Epithelium and Epidermis Models

2017

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Human eyes and skin are frequently exposed to chemicals accidentally or on purpose due to their external location. Therefore, chemicals are required to undergo the evaluation of the ocular and dermal irritancy for their safe handling and use before release into the market. Draize rabbit eye and skin irritation test developed in 1944, has been a gold standard test which was enlisted as OECD TG 404 and OECD TG 405 but it has been criticized with respect to animal welfare due to invasive and cruel procedure. To replace it, diverse alternatives have been developed: (i) For Draize eye irritation test, organotypic assay, in vitro cytotoxicity-based method, in chemico tests, in silico prediction model, and 3D reconstructed human cornea-like epithelium (RhCE); (ii) For Draize skin irritation test, in vitro cytotoxicity-based cell model, and 3D reconstructed human epidermis models (RhE). Of these, RhCE and RhE models are getting spotlight as a promising alternative with a wide applicability domain covering cosmetics and personal care products. In this review, we overviewed the current alternatives to Draize test with a focus on 3D human epithelium models to provide an insight into advancing and widening their utility.

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Identification of cornifelin and early growth response-1 gene as novel biomarkers for in vitro eye irritation using a 3D reconstructed human cornea model MCTT HCE™

Cited by 13 publications

References 22 publications

Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCE^TM

Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCE^TM

In vitro reconstructed 3D corneal tissue models for ocular toxicology and ophthalmic drug development

Alternatives toIn VivoDraize Rabbit Eye and Skin Irritation Tests with a Focus on 3D Reconstructed Human Cornea-Like Epithelium and Epidermis Models

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Identification of cornifelin and early growth response-1 gene as novel biomarkers for in vitro eye irritation using a 3D reconstructed human cornea model MCTT HCE™

Cited by 13 publications

References 22 publications

Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCETM

Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCETM

In vitro reconstructed 3D corneal tissue models for ocular toxicology and ophthalmic drug development

Alternatives toIn VivoDraize Rabbit Eye and Skin Irritation Tests with a Focus on 3D Reconstructed Human Cornea-Like Epithelium and Epidermis Models

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Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCE^TM

Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCE^TM