Vanin Joel, Getz Michael, Mahony Catherine, Knudsen Thomas B, Glazier James A
Department of Intelligent Systems Engineering and Biocomplexity Institute, Indiana University, Bloomington, IN.
Procter & Gamble Technical Centre, Reading, United Kingdom.
bioRxiv. 2025 Aug 14:2025.08.11.669602. doi: 10.1101/2025.08.11.669602.
To develop a computational model that addresses limitations in current ocular irritation assessment methods, particularly regarding long-term effects, and recovery patterns following chemical exposure or trauma to the cornea.
V-Cornea is an agent-based computer simulation implemented in CompuCell3D that models corneal epithelial homeostasis and injury response. The model incorporates biologically-inspired rules governing cell behaviors (proliferation, differentiation, death) and key signaling pathways including Epidermal Growth Factor (EGF), translating cell-level behaviors to tissue-level outcomes ( to extrapolation, IVIVE).
V-Cornea successfully reproduces corneal epithelial architecture and maintains tissue homeostasis over extended simulated periods. Following simulated trauma or toxicant exposure, the model accurately predicts healing timeframes of 3-5 days for slight and mild injuries. For moderate injuries with basement membrane disruption, the model demonstrates longer recovery times and emergent dynamic structural disorganization that mimics recurrent corneal erosions, providing mechanistic insights into these pathological conditions.
V-Cornea's modular CompuCell3D implementation is easily extensible to incorporate additional recovery and injury mechanisms. Future versions will include more realistic basement membrane dynamics and explicit representation of stromal tissue and immune response to improve predictivity for moderate injuries. This virtual-tissue approach shows potential not only for toxicological assessments but also for drug discovery and therapy optimization by providing a platform to test interventions and predict outcomes across various injury scenarios.
开发一种计算模型，以解决当前眼刺激评估方法中的局限性，特别是关于长期影响以及化学物质暴露或角膜创伤后的恢复模式。
V-Cornea是一种基于代理的计算机模拟，在CompuCell3D中实现，用于模拟角膜上皮稳态和损伤反应。该模型纳入了控制细胞行为（增殖、分化、死亡）的生物学启发规则以及包括表皮生长因子（EGF）在内的关键信号通路，将细胞水平的行为转化为组织水平的结果（外推法、体外外推法）。
V-Cornea成功再现了角膜上皮结构，并在延长的模拟时间段内维持组织稳态。在模拟创伤或接触毒物后，该模型准确预测了轻度和中度损伤的愈合时间为3至5天。对于伴有基底膜破坏的中度损伤，该模型显示出更长的恢复时间以及出现类似复发性角膜糜烂的动态结构紊乱，为这些病理状况提供了机制性见解。
V-Cornea的模块化CompuCell3D实现易于扩展，以纳入额外的恢复和损伤机制。未来版本将包括更逼真的基底膜动态以及基质组织和免疫反应的明确表示，以提高对中度损伤的预测能力。这种虚拟组织方法不仅在毒理学评估方面显示出潜力，而且通过提供一个测试干预措施并预测各种损伤情况结果的平台，在药物发现和治疗优化方面也具有潜力。
