Genome-wide transcriptional responses of human choroidal endothelial cells to corticosteroids as a model for central serous chorioretinopathy

Abstract

Purpose : Corticosteroids are a strong risk factor for central serous chorioretinopathy (CSC). However, the underlying pathophysiological mechanisms are unclear. CSC has been proposed to result from choroidal hyperpermeability. Therefore, choroidal endothelial cells (CECs), which are important for barrier function, are of particular interest. This study describes the effect of cortisol on human CECs, in order to identify potential target genes involved in CEC hyperpermeability as seen in CSC patients.

Methods : Human CECs from 10 individuals (5 males, 5 females) were isolated from cadaveric anonymous donor eyes by magnetic-activated cell sorting. Cells were treated with either cortisol (10^-6 M) or vehicle (0.01% ethanol) medium, and subsequently whole transcriptome analysis was performed on a Novaseq Illumina platform.

Results : Bioinformatic analysis showed upregulation of 153 genes and downregulation of 169 genes. Classical corticosteroid target genes were upregulated in human CECs and included FKBP5 (log2 fold change 6.8) and TSC22D3 (log2 fold change 4.5). The strongest induced gene by cortisol was ZBTB16 (log2 fold change 7.0).

Conclusions : In summary, this study describes 322 genes regulated by cortisol in primary human CECs. This includes classical corticosteroid target genes, but also a subset of these genes that has been previously linked to endothelial cell dysfunction. Functional assays based on genes of interest found in this study may help to expand the understanding of mechanisms behind the induction of CEC hyperpermeability by corticosteroids, as observed in CSC patients.

This is a 2021 ARVO Annual Meeting abstract.