The Effect of Corticosteroids on Human Choroidal Endothelial Cells: A Model to Study Central Serous Chorioretinopathy

Brinks, Joost; Dijk, Elon H. C. van; Habeeb, Mahmoud; Nikolaou, Aikaterini; Tsonaka, Roula; Peters, H.A.B.; Sips, Hetty C M; Merbel, A.F. van de; Jong, Eiko K. de; Notenboom, Robbert G E; Kiełbasa, Szymon M.; Maarel, Silvère M. van der; Quax, Paul H.A.; Meijer, Onno C.; Boon, Camiel J F

doi:10.1167/iovs.18-25054

Cited by 21 publications

(21 citation statements)

References 47 publications

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“…It has been shown that glucocorticoids are involved in the pathogenesis of CSC, and glucocorticoid receptors are expressed both in the choroid and retina (Zhao et al 2010; Brinks et al 2018). In rats and humans, corticosterone may cause choroidal thickening, a feature typical for patients with CSC (Zhao et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Altered plasma cytokine levels in acute and chronic central serous chorioretinopathy

Karska‐Basta

Pociej‐Marciak

Chrząszcz

et al. 2020

Acta Ophthalmologica

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Purpose To evaluate plasma levels of selected cytokines and investigate their correlation with choroidal thickness (CT) in patients with acute and chronic central serous chorioretinopathy (CSC). Methods We enrolled 30 patients with acute CSC, 30 patients with chronic CSC and 20 controls. Plasma concentrations of 12 cytokines, interleukins IL‐8, IL‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐10 and IL‐12 p70, granulocyte‐macrophage colony‐stimulating factor, interferon‐γ, tumour necrosis factor‐α (TNF‐α) and vascular endothelial growth factor (VEGF), were measured using multiplex immunoassays. Differences in cytokine levels between groups were assessed. We also investigated correlations between cytokine levels and CT using swept‐source optical coherence tomography, as well as an association between plasma cytokine profile and systemic hypertension. Results We noted differences in IL‐6 (p = 0.005), IL‐10 (p = 0.03), IL‐12 p70 (p = 0.028) and VEGF (p = 0.029) levels between groups. Pro‐inflammatory IL‐12 p70 and multidirectional IL‐10 cytokines were upregulated, while pro‐angiogenic VEGF was downregulated in chronic CSC as compared with controls (p = 0.005, p = 0.025 and p = 0.027, respectively). Interleukin‐6 (IL‐6) was upregulated in acute and chronic CSC (p = 0.030 and p = 0.005, respectively). Interleukin‐5 (IL‐5), IL‐6 and IL‐12 levels correlated with mean CT in acute CSC (p = 0.008, p = 0.003 and p = 0.044, respectively), while IL‐8, IL‐6 and TNF‐α plasma levels correlated with hypertension in chronic CSC (p = 0.005, p = 0.033 and p = 0.001, respectively). Conclusion We provided new evidence for the possible role of plasma cytokines in the pathogenesis of CSC. Our results suggest that IL‐6 may be important in the pathophysiology of acute and chronic CSC. The association between inflammatory response and hypertension in patients with CSC was also confirmed.

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Section: Discussionmentioning

confidence: 99%

Altered plasma cytokine levels in acute and chronic central serous chorioretinopathy

Karska‐Basta

Pociej‐Marciak

Chrząszcz

et al. 2020

Acta Ophthalmologica

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“…Furthermore, high levels of endogenous corticosteroids as found in Cushing’s syndrome are associated with CSC ( 18-21 ). In line with these findings, both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), the 2 corticosteroid-binding receptors, have been postulated to play a role in CSC pathogenesis ( 1 , 4 , 22 , 23 ). Another peculiarity of CSC is that males are predominantly affected, representing approximately 85% of the cases, which may point to a role for androgens ( 17 ).…”

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confidence: 83%

“…Human primary CECs were isolated as described previously ( 22 ). Briefly, the central region of the RPE/choroid complex was dissected from the donor eyes and incubated for 60 min in 0.05% trypsin-EDTA in a shaking water bath at 37°C.…”

Section: Methodsmentioning

confidence: 99%

The Cortisol Response of Male and Female Choroidal Endothelial Cells: Implications for Central Serous Chorioretinopathy

Brinks

Dijk

Kiełbasa

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Central serous chorioretinopathy (CSC) is a severe ocular disease characterized by fluid accumulation under the retina and abnormalities in the underlying vascular layer, the choroid. CSC has a striking prevalence in males of 80-90% of total patients. Corticosteroids are the most pronounced extrinsic risk factor for CSC. Choroidal endothelial cells (CECs) are important for the vascular integrity of the choroid, but the effects of corticosteroid effects in these cells are unknown. Design and Objective We aimed to reveal the potential steroidal contribution to CSC. We characterized the expression of the glucocorticoid-, mineralocorticoid-, and androgen receptor in the human choroid, using immunohistochemistry. Using RNA-sequencing, we describe the cortisol response in human CECs derived from 5 male and 5 female postmortem donors. Results The glucocorticoid receptor was highly expressed in the human choroid, whereas no to minimal expression of the mineralocorticoid- and androgen receptors was observed. The extensive transcriptional response to cortisol in human primary cultured CECs showed interindividual differences, but very few sex differences. Several highly regulated genes such as ZBTB16 (log2 fold change males 7.9; females 6.2) provide strong links to choroidal vascular regulation. Conclusions The glucocorticoid receptor predominantly mediates the response to cortisol in human CECs. Interindividual differences are an important determinant regarding the cortisol response in human cultured CECs, whereas intrinsic sex differences appear less pronounced. The marked response of particular target genes in endothelial cells to cortisol, such as ZBTB16, warrants further investigation into their potential role in the pathophysiology of CSC and other vascular conditions.

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“…Endothelial cells are involved in maintaining the integrity of blood vessel walls and controlling the transfer of molecules. Choroidal endothelial cells have been cultured from human donors and both corticosteroids and mineralocorticoids administered (Brinks et al 2018). The resultant changes in gene expression were then measured using the reverse-transcriptase polymerase chain reaction (RT-PCR).…”

Section: The Corticosteroid Hypothesis and Information From Cell Biology Studiesmentioning

confidence: 99%

Central serous chorioretinopathy: An update on risk factors, pathophysiology and imaging modalities

Kaye

Chandra

Sheth

et al. 2020

Progress in Retinal and Eye Research

164

216

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The Effect of Corticosteroids on Human Choroidal Endothelial Cells: A Model to Study Central Serous Chorioretinopathy

Cited by 21 publications

References 47 publications

Altered plasma cytokine levels in acute and chronic central serous chorioretinopathy

Altered plasma cytokine levels in acute and chronic central serous chorioretinopathy

The Cortisol Response of Male and Female Choroidal Endothelial Cells: Implications for Central Serous Chorioretinopathy

Central serous chorioretinopathy: An update on risk factors, pathophysiology and imaging modalities

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