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Developing an in silico Virtual Cornea for Predictive Toxicology
Citation:
Glazier, J., J. Vanin, C. Mahony, AND T. Knudsen. Developing an in silico Virtual Cornea for Predictive Toxicology. 12th World Congress on Alternatives and Animal Use in the Life Sciences (WC12), Niagra, Ontario, CANADA, August 27 - 31, 2023. https://doi.org/10.23645/epacomptox.25678230
Impact/Purpose:
This abstract reflects a collaborative study to build a cell-based computational (in silico) model of the cornea (vCornea) to be used for predictive toxicology. The abstract was invited to the symposium on 'The future of multi-scale modelling and simulation in human disease and toxicology' for presentation at the 12th World Congress on Alternatives and Animal Use in the Life Sciences (WC12) in Aug 2023.
Description:
Toxicological outcomes in vivo result from complex interactions among molecular, cellular and tissue-level damage responses which are difficult to recapitulate in vitro or extrapolate from data-based Machine Learning or molecular-level computer simulations. Mechanistic multiscale, multicellular computer simulations, known as Virtual Tissues (VTs), predict systems-level in vivo toxicological outcomes from the detailed molecular and cellular information provided by in vitro assays and have been applied successfully by the US EPA in a variety of toxicological contexts (e.g. cleft palate and zonal liver damage on exposure to toxicants). Because of its experimental accessibility for in vitro culture, its relative structural and functional simplicity and its importance in toxicity assays, we have initiated a collaborative effort to develop a Virtual Toxicological Cornea. The simulation, implemented in the open-source CompuCell3D modeling framework, simulates the main cell types in the corneal epithelium and simplified representations of the feedback controlling cell proliferation, differentiation and damage. Subsequent versions will include additional intracellular and intercellular molecular signaling pathways, immune cells, tear film transport and vascular remodeling and transport. Our aim is to successfully recapitulate exposure to a variety of toxicants at different loci and intensities and predict critical outcomes including full recovery, loss of structural integrity and the development of opacity. Developing and validating a VTCornea which correctly predicts structure, function, homeostasis and damage will establish a core set of principles for the development of VTs for other organ systems to complement in vitro testing for toxicological assessment. Disclaimer: This abstract does not necessarily reflect USEPA policy.
URLs/Downloads:
DOI: Developing an in silico Virtual Cornea for Predictive Toxicology
GLAZIER_WC12_PRESENTATION_FINAL.PDF (PDF, NA pp, 8584.125 KB, about PDF)