Keratoconus (KC) is a bilateral corneal dystrophy and a multifactorial, multigenic disorder with an etiology involving a strong environmental component and complex inheritance patterns. The underlying pathophysiology of KC is poorly understood because of potential crosstalk between genetic–epigenetic variants possibly triggered by the environmental factors. Here, we decode the etiopathological basis of KC using genomic, transcriptomic, proteomic and metabolic approaches. The lack of relevant models that accurately imitate this condition has been particularly limiting in terms of the effective management of KC. Tissue-engineered in vitro models of KC could address this need and generate valuable insights into its etiopathology for the establishment of disease models to accelerate drug discovery.

圆锥角膜病（KC）是一种双侧角膜营养不良，是一种多因素，多基因的疾病，其病因涉及强大的环境成分和复杂的遗传模式。由于可能由环境因素触发的遗传表观遗传变异之间存在潜在的串扰，因此人们对KC的潜在病理生理学了解甚少。在这里，我们使用基因组学，转录组学，蛋白质组学和代谢学方法对KC的病因学基础进行解码。缺乏准确模仿这种情况的相关模型，尤其是在有效控制KC方面受到了限制。组织工程化的KC体外模型可以满足这一需求，并对其病因学产生有价值的见解，以建立疾病模型以加速药物发现。