Ocular Surface Inflammation: Bioengineered 3D model of Human Conjunctiva

Inflammatory ocular surface diseases are very prevalent among the global population. Patients demand more efficacious, new treatments for their diseases and, at the same time, governments and pharmaceutical companies are concerned about the cost of the research needed to develop new drugs. The increasing use of three-dimensional models has shown their utility in decreasing research costs by providing more reliable results and reducing the use of animals in research.

The conjunctiva is involved in different ocular surface diseases, playing an active role in the pathophysiology of common conditions such as dry eye disease, Sjögren's syndrome, and allergic conjunctivitis, among others. To date, the majority of in vitro investigations concerning the conjunctival tissue have been carried out using monolayer culture techniques that do not recapitulate the complexity of the whole tissue.

For these reasons, we have developed a three-dimensional model of the human conjunctiva that can be used to perform pathophysiology experiments and test drug response. Briefly, fibrin-based matrices (derived from human plasma or plasma cryoprecipitate) were used as scaffolds, and primary cells obtained from cadaveric conjunctival tissue were seeded (fibroblast inside and epithelial cells on the surface). Characterization of conjunctival constructs showed epithelial cell stratification, cell polarization and functionality. Conditions such as desiccation and exposure to IL-13 were used to in vitro mimic dry eye disease or allergy. In response to those stimuli, conjunctival constructs increased IL-6 and MUC5AC production. Therefore, this three-dimensional model can be used to study ocular inflammatory diseases and test novel therapies.