In vitro model for Fuchs Endothelial Dystrophy and its effects on corneal endothelial cells

Abstract

Fuchs endothelial dystrophy (FED), a corneal endothelium disease, is one of the leading causes for corneal transplantation. During disease progression, Descemet membrane’s (DM), the corneal endothelial basement membrane, biomechanical properties such as surface topography and stiffness are affected and form guttatas, pillar-like structures, with different geometries and varied stiffness. Corneal endothelial cells become apoptotic and their function is severely hampered. However, the impact of FED guttatas and stiffness on human corneal endothelial cells remains poorly understood. Currently, endothelial cell injection therapy is being developed and the effects of biomechanical cues on cell therapy is largely unknown. Hence, I hypothesized that guttatas and stiffness might affect corneal endothelial cell behavior such as increasing cell apoptosis. The impact of synthetic guttatas (s-guttata) dimensions on corneal endothelial cell behaviour in endothelial cell injection therapy conditions was studied. A significant increase in the cell apoptosis was observed across 20 µm height s-guttatas on different days. S-Guttatas with higher diameter or spacings showed significant late stage apoptosis and the increasing trend was observed in s-guttatas with lower dimensions. Furthermore, these apoptotic cells were localized around the s-guttatas; and the apoptotic population was the highest in the pattern with lower diameter and spacing. Cells surrounding s-guttatas had higher cytoskeletal stress. In addition, preliminary studies on the stiffness of DM was also performed. Cumulatively, FED guttatas have the potential to induce apoptosis.