Interpreting the role of cortisol and steroid receptors in central serous chorioretinopathy
Abstract
My thesis expands our current knowledge on the pathogenesis of central serous chorioretinopathy (CSC) from an experimental perspective. CSC is a posterior eye disease that has higher prevalence in males than females. Corticosteroid exposure is well-known risk factor. However, the underlying CSC pathogenesis is still unclear. Based on the clinical hallmarks of CSC, choroidal endothelial cells are likely to be affected. In this thesis, we use postmortem- or patient-derived samples to address this problem. The first research chapter describes the abundance of sex-steroid receptors in the human choroid tissue across sex and age using a standardized staining procedure. The second research chapter focuses on the transcriptomic response of CSC patient-derived human induced pluripotent stem cells-derived endothelial cells (hiPSC-ECs). Through bulk-RNA sequencing, we explore the differences between patient-derived hiPSC-ECs versus control lines. The third research chapter explores the role of cortisol target gene, ZBTB16, in the glucocorticoid-mediated action. ZBTB16 is initially thought to be involved in the pathogenesis of CSC, however, the data showed no differences in response between control- and patient-derived cells. This last research chapter describes the role of ZBTB16 in limiting glucocorticoid receptor (GR) transactivation and potentiating GR transrepression, which may be relevant in inflammatory settings.
