Corneal epithelium models for safety assessment in drug development: Present and future directions

Abdalkader, Rodi Kado; Fujita, Takuya

doi:10.1016/j.exer.2023.109697

Cited by 2 publications

(1 citation statement)

References 154 publications

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“…To ethically reduce the usage of animals in experiments, there is a growing emphasis on embracing the 3 Rs, the principles of Refinement, Reduction, and Replacement [18,19]. An in vitro experimental system employing corneal epithelial cell lines has emerged as a valuable tool for understanding ocular events [20]. It is important to recognize that although these models are valuable tools, they are currently unable to completely replace animal experiments.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory Cytokines and Chemokines Are Synergistically Induced in a ROS-Dependent Manner by a Co-Culture of Corneal Epithelial Cells and Neutrophil-like Cells in the Presence of Particulate Matter

Zeng,

Yoshida,

Wang

et al. 2024

Antioxidants

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Ocular exposure to particulate matter (PM) causes local inflammation; however, the influence of neutrophils on PM-induced ocular inflammation is still not fully understood. In this study, we constructed a system to investigate the role of PM in ocular inflammation using a co-culture of human corneal epithelial cells (HCE-T) and differentiation-induced neutrophils (dHL-60). To investigate whether HCE-T directly endocytosed PM, we performed a holographic analysis, which showed the endocytosis of PM in HCE-T. The cytokines and chemokines produced by HCE-T were measured using an ELISA. HCE-T treated with PM produced IL-6 and IL-8, which were inhibited by N-Acetyl-L-cysteine (NAC), suggesting the involvement of ROS. Their co-culture with dHL-60 enhanced their production of IL-6, IL-8, and MCP-1. This suggests an inflammatory loop involving intraocular corneal epithelial cells and neutrophils. These cytokines and chemokines are mainly regulated by NF-κB. Therefore, this co-culture system was examined in the presence of an IKK inhibitor known to downregulate NF-κB activity. The IKK inhibitor dramatically suppressed the production of these factors in co-culture supernatants. The results suggest that the inflammatory loop observed in the co-culture is mediated through ROS and the transcription factor NF-κB. Thus, the co-culture system is considered a valuable tool for analyzing complex inflammations.

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Section: Introductionmentioning

confidence: 99%

Inflammatory Cytokines and Chemokines Are Synergistically Induced in a ROS-Dependent Manner by a Co-Culture of Corneal Epithelial Cells and Neutrophil-like Cells in the Presence of Particulate Matter

Zeng,

Yoshida,

Wang

et al. 2024

Antioxidants

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Establishment of human corneal epithelial organoids for ex vivo modelling dry eye disease

Wan,

Gu,

Zhou

et al. 2024

Cell Proliferation

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Dry eye disease (DED) is a growing public health concern affecting millions of people worldwide and causing ocular discomfort and visual disturbance. Developing its therapeutic drugs based on animal models suffer from interspecies differences and poor prediction of human trials. Here, we established long‐term 3D human corneal epithelial organoids, which recapitulated the cell lineages and gene expression signature of the human corneal epithelium. Organoids can be regulated to differentiate ex vivo, but the addition of FGF10 inhibits this process. In the hyperosmolar‐induced DED organoid model, the release of inflammatory factors increased, resulting in damage to the stemness of stem cells and a decrease in functional mucin 1 protein. Furthermore, we found that the organoids could mimic clinical drug treatment responses, suggesting that corneal epithelial organoids are promising candidates for establishing a drug testing platform ex vivo. In summary, we established a functional, long‐term 3D human epithelial organoid that may serve as an ex vivo model for studying the functional regulation and disease modelling.

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Corneal epithelium models for safety assessment in drug development: Present and future directions

Cited by 2 publications

References 154 publications

Inflammatory Cytokines and Chemokines Are Synergistically Induced in a ROS-Dependent Manner by a Co-Culture of Corneal Epithelial Cells and Neutrophil-like Cells in the Presence of Particulate Matter

Inflammatory Cytokines and Chemokines Are Synergistically Induced in a ROS-Dependent Manner by a Co-Culture of Corneal Epithelial Cells and Neutrophil-like Cells in the Presence of Particulate Matter

Establishment of human corneal epithelial organoids for ex vivo modelling dry eye disease

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