Establishing and validation of a human cornea-on-chip for preclinical drug development.

The cornea is a barrier that protects the eye from the outside world and likewise hampers drug absorption. Most ophthalmic medicine is washed away during instillation and is absorbed into systemic circulation. This is especially relevant when considering the main target population, the elderly, which also have an increased susceptibility to adverse drug reactions due to polypharmacy and decreased renal function. Hence, new topical formulations require rigorous testing to ensure therapeutic efficacy, while keeping local and systemic toxicity to a minimum. However, promising preclinical results are often not corroborated during human testing because available corneal models have poor predictive power. Traditional 2D culture fails to recapitulate complex tissues such as the cornea while animal models exhibit interspecies differences that limit translatability of results to humans. Organs-on-chips, which are rationally-designed microfluidic chips that contain artificial tissue, hold the promise of improving the status quo. While organ-on-chip technology has already proven its merits in certain fields, in the context of the cornea it remains relatively unexplored. This project proposal outlines the development of the first cornea-on-chip that comprises every cellular layer – epithelium, stroma and endothelium – of the cornea, exposed to the dynamics of an artificial tear film on one side and connected to an artificial anterior chamber on the other.

Keywords:OPHTHALMOLOGY, CORNEA, ORGAN-ON-CHIP, IN VITRO MODEL

Disciplines:Microfluidics/flow chemistry, Tissue engineering, Ophthalmology, Pharmacokinetics, Cellular interactions and extracellular matrix

Project type:Collaboration project