Modeling diabetic epitheliopathy using 3D-Organotypic corneal epithelium

Abstract

Diabetic keratopathy (DK) is a degenerative corneal disease occurring in more than 50 % of diabetic patients. DK is correlated with the hyperglycemic state causing morphological and functional changes in corneal layers. Currently, most studies on the cornea are performed on two-dimensional (2D) cultures in vitro or animal models. Although 2D culture models can provide large amounts of data at low cost, they poorly represent the complex pathophysiology of the human cornea and hardly predict in vivo responses that can be achieved with animal model studies. However, the use of the latter presents ethical problems. Therefore, it is necessary to identify new strategies and models that can integrate the information validly and effectively, to reduce the number of animals used. Here, we used human corneal epithelial cells (hCECs) derived from donor cornea differentiated into three-dimensional (3D)-organotypic air-liquid interface (ALI), which resemble the features of the corneal epithelium. The 3D-organotypic ALI corneal epithelium was subjected to high-glucose conditions to generate a model of diabetic epitheliopathy. Our model showed well-established molecular and cellular characteristics of this pathology, such as epithelial defects and inflammation, with increased expression of IL-1β, TNF-$\alpha$, p-NF-kB, COX-2, MMP-2 and MMP-9. The data provided highlight the utility of 3D-organotypic corneal epithelium in modeling diabetic epitheliopathy, offering new avenues in drug screening, as well as in precision and personalized medicine.