Advanced 3D model of the Human Cornea for Keratoconus

Project Summary/Abstract: The cornea, the tissue that makes up the front of the eye acts as a barrier between the environment and the eye and focuses light onto the lens and then to the retina. Degradation of the cornea, commonly found in keratoconus (KC), leads to progressive vision loss requiring ever increasing prescriptive correction and historically culminating in corneal transplant. Despite the rise of the corneal crosslinking procedure to slow degradation, little is known about the etiology of KC and/or the long-term effects of the crosslinking procedure on KC, including its long-term efficacy. In combination with a lack of in vivo models that accurately reflect KC, there is a lack of commercial corneal models on the market. Current models, such as Mattek’s EpiOcular and EpiCornea consist purely of corneal epithelial cells and are aimed at basic drug transport and irritation studies. While academic models are significantly more advanced, recapitulating multiple cell types, none of the models recapitulate corneal curvature. Further, few models incorporate flow analogous to the that of the tear film and aqueous humor: the tear film represents a rich source of biomarkers that can be easily sampled non-invasively and aqueous humor generates the pressure force that maintains the shape of the eye. Therefore there is a need to recapitulate flow and forces in corneal models. Overall there is a lack of physiological relevance in commercially available cornea models and a need for a more advanced in vitro model. We propose to develop a model that meets these needs. The key innovations of this model will be 1) the incorporation of corneal geometry, and incorporation of 2) flow (tear film) and 3) pressure effects (IOP). The Phase I effort will focus on providing a proof of concept for these key innovations. The phase II will focus on demonstrating the model validity for KC through extensive comparison between healthy and KC diseased models derived from KC patient cells. The model will be marketed initially to the KC research community for basic research studies and pharmaceutical companies evaluating crosslinking and other KC therapeutics and then extended to sales to the general corneal drug and research market.