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

Abstract

The human corneal epithelial barrier plays a crucial role in drug testing studies, including drug absorption, distribution, metabolism, and excretion (ADME), as well as toxicity testing during the preclinical stages of drug development. However, despite the valuable insights gained from animal and current in vitro models, there remains a significant discrepancy between preclinical drug predictions and actual clinical outcomes. Additionally, there is a growing emphasis on adhering to the 3R principles (refine, reduce, replace) to minimize the use of animals in testing. To tackle these challenges, there is a rising demand for alternative in vitro models that closely mimic the human corneal epithelium. Recently, remarkable advancements have been made in two key areas: microphysiological systems (MPS) or organs-on-chips (OoCs), and stem cell-derived organoids. These cutting-edge platforms integrate four major disciplines: stem cells, microfluidics, bioprinting, and biosensing technologies. This integration holds great promise in developing powerful and biomimetic models of the human cornea.

Keywords: Corneal epithelial barrier; Drug development; Organ-on-a-chip; Stem cells.