Novel phototoxicity assay using human embryonic stem cell-derived retinal pigment epithelial cells

Purpose: There has been a recent explosion in the variety of techniques used to accomplish corneal cross-linking (CXL) for the treatment of ectatic corneal diseases. To understand the success or failure of various techniques, we review the physicochemical basis of corneal CXL and re-evaluate the current principles and long-standing conventional wisdom in the light of recent, compelling, and sometimes contradictory research. Methods: Two clinicians and a medicinal chemist developed a list of current key topics, controversies, and questions in the field of corneal CXL based on information from current literature, medical conferences, and discussions with international practitioners of CXL. Results: Standard corneal CXL with removal of the corneal epithelium is a safe and efficacious procedure for the treatment of corneal ectasias. However, the necessity of epithelium removal is painful for patients, involves risk and requires significant recovery time. Attempts to move to transepithelial corneal CXL have been hindered by the lack of a coherent understanding of the physicochemistry of corneal CXL. Misconceptions about the applicability of the Bunsen–Roscoe law of reciprocity and the Lambert–Beer law in CXL hamper the ability to predict the effect of ultraviolet A energy during CXL. Improved understanding of CXL may also expand the treatment group for corneal ectasia to those with thinner corneas. Finally, it is essential to understand the role of oxygen in successful CXL. Conclusions: Improved understanding of the complex interactions of riboflavin, ultraviolet A energy and oxygen in corneal CXL may provide a successful route to transepithelial corneal CXL.

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Corneal Cross-Linking: The Science Beyond the Myths and Misconceptions

Rubinfeld

Caruso

Ostacolo

2019

Cornea

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Development of alternatives to animal experiments using pluripotent stem cells

Saito

Suzuki

Kobayashi

2018

Folia Pharmacol. Jpn.

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Animal experiments have occupied an important position in the safety assessment of chemicals. However, due to the rise in animal welfare as seen in the ban of animal experiments in European cosmetic development, the development of alternative methods for animal experiments has become very important in recent years. Development of in vitro tests for local toxicity such as irritation and sensitization tests is preceded. Meanwhile, alternative tests for systemic toxicity such as chronic and developmental toxicities are under development. In developing alternative methods using cultured cells, we have been focusing on pluripotent stem cells such as ES and iPS cells and studying alternatives to developmental toxicity and neurotoxicity. As an alternative test of developmental toxicity, we developed the Hand 1-Luc EST, which is a simple test utilizing cardiomyocyte differentiation process of mouse ES cells, and Tubb 3- and Reln-Luc ESTs using nerve differentiation process. Recently, it was clarified that the combination of the Hand 1-Luc EST and the Tubb 3- and Reln-Luc ESTs improves the prediction of the developmental toxicity. In the study of in vitro neurotoxicity test using neurons derived from mouse ES cells, evaluation methods for neurite outgrowth using high-content imaging technology and for neural function using multi-electrode arrays were developed. In addition, we introduce differentiation methods for retinal tissues from human ES/iPS cells, which are the results as the collaboration with RIKEN and the present state of an in vitro phototoxicity test using retinal pigment epithelial cells (RPE) derived from human ES cells.

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Lack of human relevance for rat developmental toxicity of flumioxazin is revealed by comparative heme synthesis assay using embryonic erythroid cells derived from human and rat pluripotent stem cells

et al. 2022

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Novel phototoxicity assay using human embryonic stem cell-derived retinal pigment epithelial cells

Cited by 3 publications

References 32 publications

Corneal Cross-Linking: The Science Beyond the Myths and Misconceptions

Corneal Cross-Linking: The Science Beyond the Myths and Misconceptions

Development of alternatives to animal experiments using pluripotent stem cells

Lack of human relevance for rat developmental toxicity of flumioxazin is revealed by comparative heme synthesis assay using embryonic erythroid cells derived from human and rat pluripotent stem cells

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