Design and development of an in vitro tear replenishment system.

Understanding the cellular and molecular mechanisms of the corneal tissue and translating them into effective therapies requires organotypic culture systems that can better model the physiological conditions of the front of the eye. Human corneal in vitro models currently exist, however, the lack of tear replenishment limits corneal in vitro models' ability to accurately simulate the physiological environment of the human cornea. The tear replenishment system (TRS), a micro-fluidic device, was developed to mimic the in vivo tear replenishment in the human eye in an in vitro corneal model. The TRS is capable of generating adjustable intermittent flow from 0.1 µL in every cycle. The TRS is a sterilizable device that is designed to fit standard 6-well cell culture plates. Experiments with the corneal models demonstrated that exposure to the TRS did not damage the integrity of the stratified cell culture. Contact lenses "worn" by the in vitro corneal model also remained moist at all times and the cytotoxicity of BAK could also be verified using this model. These in vitro results confirmed that the TRS presents novel avenues to assess lens-solution biocompatibility and drug delivery systems in a physiologically relevant milieu.