Abstract
The cornea, the anterior meniscus-shaped transparent and refractive structure of the ocular globe, is the first mechanical barrier of the eye. The functions of the cornea are largely dependent on the health of its endothelium. The current gold standard to treat the worldwide blindness caused by corneal endothelial cells (CECs) failure is the allogeneic corneal transplantation by using healthy cadaveric donor corneas to restore corneal transparency. The main goal of cornea organ culture (OC) in eye banks is the maintenance of the endothelial cell density (ECD) and the barrier function of the endothelium, both crucial parameters in transplantation outcomes. Cornea is not subjected to the multiple mechanical cues during OC such as the hydrokinetic pressure of the aqueous humor and intraocular pressure (IOP). YAP (Yes Associated Protein), a key transcriptional coactivators, is known for sensing diverse biomechanical cues and transducing them into biological outcomes, specific for each cell type and mechanical force. The biomechanical cues regulating YAP in human corneal endothelium remain unidentified. Therefore, we investigated the expression and the subcellular localization of YAP in the endothelium of OC corneas. We demonstrated that biomechanical parameters such as CEC geometry, ECD and cell-cell interaction, specifically and differentially regulate the expression, the subcellular localization and phosphorylation of YAP. Therefore, understanding the impact of these biophysical cues may enable the identification of biomechanics-associated molecules capable of promoting homeostasis and functions of CECs. This, in turn, could pave the way for improved corneal conservation in eye banks and new pharmacological treatments for endothelial insufficiencies.
