Cortisol-modulated Barrier Properties of Cultured Choroidal Endothelial Cells: a Model to Study Central Serous Chorioretinopathy

Abstract

Purpose : Choroidal hyperpermeability, as seen on multimodal imaging in central serous chorioretinopathy (CSC) patients, is a sign of an impaired barrier function of choroidal vasculature. However, its etiology and pathogenesis in CSC is poorly understood. Corticosteroids are a major risk factor for CSC. Here, we studied the effect of cortisol on the barrier function in an experimental model using choroidal endothelial cells (CECs), as a cell type regulating choroidal vascular permeability and vascular tone.

Methods : Human CECs were isolated and purified from eyes of 2 independent non-CSC donors. The cells were cultured in transwell inserts and treated with increasing concentrations of cortisol or vehicle, and in the presence or absence of the glucocorticoid receptor antagonist mifepristone for 24 hours. Trans-endothelial electrical resistance (TEER) and capacitance (C_cl), parameters of barrier function, were measured in real-time with a CellZscope® system. Endothelial permeability was measured at the end of the treatment using different size of fluorescently labelled tracer molecules (70 kDa and 766 Da).

Results : CECs formed a permeable barrier as indicated by a low TEER value. Cortisol dose-dependently increased the TEER and simultaneously decreased the C_cl values. In addition, cortisol significantly reduced the permeability of fluorescent tracers. The barrier response of CECs to cortisol were dampened by mifepristone treatment, suggesting a glucocorticoid receptor-mediated effect.

Conclusions : The response of CECs to cortisol leads to increased barrier integrity and decreased endothelial permeability, which resembles the response of endothelial cells in other vascular beds. The current model may be suitable to study the pathophysiology of CSC and other diseases associated with an impairment of CEC’s barrier integrity.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.