July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Corticosteroids and central serous chorioretinopathy: the role of the mineralocorticoid and glucocorticoid receptor in human choroidal endothelial cells
Author Affiliations & Notes
  • Joost Brinks
    Ophthalmology, Leiden University Medical Center, Leiden, Netherlands
  • Elon H.C. van Dijk
    Ophthalmology, Leiden University Medical Center, Leiden, Netherlands
  • Onno C. Meijer
    Endocrinology, Leiden University Medical Center, Netherlands
  • Camiel Boon
    Ophthalmology, Leiden University Medical Center, Leiden, Netherlands
    Ophthalmology, Amsterdam University Medical Center, Amsterdam, Netherlands
  • Footnotes
    Commercial Relationships   Joost Brinks, None; Elon van Dijk, None; Onno Meijer, None; Camiel Boon, None
  • Footnotes
    Support  ZonMW Grant 'Meer Kennis Minder Dieren'
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4325. doi:
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      Joost Brinks, Elon H.C. van Dijk, Onno C. Meijer, Camiel Boon; Corticosteroids and central serous chorioretinopathy: the role of the mineralocorticoid and glucocorticoid receptor in human choroidal endothelial cells. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4325.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Central serous chorioretinopathy (CSC) is a chorioretinal disease of which the pathogenesis is largely unknown. Choroidal dysfunction is presumed to be underlying in CSC. Choroidal endothelial cells (CECs) are important regulators of vascular integrity, and are therefore of particular interest to study the pathophysiology of this disease. Multiple risk factors have been related to CSC, of which exposure to corticosteroids is the most pronounced. In a previous study, we have identified the glucocorticoid receptor (GR) rather than the mineralocorticoid receptor (MR) as mediator of the corticosteroid response in cultured human primary CECs. However, it was unclear whether a lack of response mediated by the MR was due to either post-mortem degradation of the protein or loss of expression due to in vitro conditions, or physiological low expression of the MR in CECs. In this study, we primarily aim to identify the role of the MR in CECs, with respect to the worldwide use of MR antagonists as treatment for CSC.

Methods : Human primary CECs were isolated from cadaveric donor eyes by enzymatic digestion and magnetic-activated cell sorting. Protein quantification of the GR and MR was performed in both directly isolated CECs and primary CECs cultured for 14 days. Immunofluorescence labelling of the GR and MR protein was performed in post-mortem human choroidal tissue. Expression of MR-specific target genes (KCNN3, KCNN4, ICAM1) was analysed in primary CECs after corticosteroid exposure, to assess whether MR-mediated effects might occur in vitro.

Results : Protein levels of the MR and the GR in directly isolated CECs were comparable to in vitro cultured CECs, with relatively low MR expression compared to the GR. Sparse MR immunoreactivity was detected in tissue sections, and MR-specific target genes were not regulated upon MR agonism or antagonism in vitro.

Conclusions : CECs express the GR and this is maintained in vitro. Interestingly, MR expression is considerably lower in all tested samples, and this does not appear to be diminished by post-mortem degradation or in vitro culture. Furthermore, MR-specific target genes of endothelial cells are not regulated in vitro upon either MR agonism or MR antagonism. In conclusion, these data support a predominant role for the GR in the corticosteroid response of CECs, whereas the role of the MR may be limited.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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