A Bioengineered Model of the Human Cornea for Preclinical Assessment of Human Ocular Exposure to Environmental Toxicants

Abstract

Here a bioengineered platform is introduced to investigate adverse effects of environmental materials on the human cornea. Using primary cells, this system is capable of reproducing the differentiated corneal epithelium and its underlying stroma in the human eye, which can then be treated with externally applied solid, liquid, or gaseous substances in a controlled manner and under physiologically relevant conditions. The proof-of-principle of how this system can be used to simulate human ocular exposure to different classes of environmental toxicants for direct visualization and quantitative analysis of their potential to induce acute corneal injury and inflammation is demonstrated. This model can also be further engineered to create an electromechanically actuated array of multiple human corneal tissues that can emulate spontaneous eye blinking. Using this advanced system, it is shown that blinking-like mechanical motions may play a protective role against adverse effects of environmental toxicants. This work yields an immediately deployable in vitro technology for screening ocular toxicity of existing and emerging environmental materials of various types and may enable the development of more realistic, human-relevant preclinical toxicology models complementary to traditional animal testing.