July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
The effect of corticosteroids on human choroidal endothelial cells: a model to study central serous chorioretinopathy
Author Affiliations & Notes
  • Elon H. Van Dijk
    Ophthalmology, Leiden University Medical Center, Leiden, Netherlands
  • Mahmoud Habeeb
    Ophthalmology, Leiden University Medical Center, Leiden, Netherlands
  • Aikaterini Nikolaou
    Ophthalmology, Leiden University Medical Center, Leiden, Netherlands
  • Joost Brinks
    Ophthalmology, Leiden University Medical Center, Leiden, Netherlands
  • Roula Tsonaka
    Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, Netherlands
  • Hendrika Peters
    Vascular Surgery, Leiden University Medical Center, Leiden, Netherlands
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands
  • Hetty Sips
    Medicine, Division of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, Netherlands
  • Arjanneke van de Merbel
    Urology, Leiden University Medical Center, Leiden, Netherlands
  • Eiko de Jong
    Ophthalmology, Radboud University Medical Center, Nijmegen, Netherlands
  • Robbert Notenboom
    Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands
  • Szymon Kielbasa
    Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, Netherlands
  • Silvère van der Maarel
    Human Genetics, Leiden University Medical Center, Leiden, Netherlands
  • Paul Quax
    Vascular Surgery, Leiden University Medical Center, Leiden, Netherlands
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands
  • Onno Meijer
    Medicine, Division of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, Netherlands
  • Camiel Boon
    Ophthalmology, Leiden University Medical Center, Leiden, Netherlands
  • Footnotes
    Commercial Relationships   Elon Van Dijk, None; Mahmoud Habeeb, None; Aikaterini Nikolaou, None; Joost Brinks, None; Roula Tsonaka, None; Hendrika Peters, None; Hetty Sips, None; Arjanneke van de Merbel, None; Eiko de Jong, None; Robbert Notenboom, None; Szymon Kielbasa, None; Silvère van der Maarel, None; Paul Quax, None; Onno Meijer, None; Camiel Boon, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1577. doi:
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      Elon H. Van Dijk, Mahmoud Habeeb, Aikaterini Nikolaou, Joost Brinks, Roula Tsonaka, Hendrika Peters, Hetty Sips, Arjanneke van de Merbel, Eiko de Jong, Robbert Notenboom, Szymon Kielbasa, Silvère van der Maarel, Paul Quax, Onno Meijer, Camiel Boon; The effect of corticosteroids on human choroidal endothelial cells: a model to study central serous chorioretinopathy
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):1577.

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

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Abstract

Purpose : Central serous chorioretinopathy is a relatively common chorioretinal disease that can lead to significant vision loss. Endogenous and exogenous hypercortisolism are the most important risk factors for central serous chorioretinopathy. The disease appears to originate in the choroid, with secondary breakdown of the retinal pigment epithelial outer blood-retinal barrier, resulting in subretinal fluid accumulation. However, the exact pathogenesis is unknown. We developed a model to allow for the investigation of corticosteroid administration to primary human choroidal endothelial cells, to unravel the role of corticosteroids in central serous chorioretinopathy.

Methods : Choroidal endothelial cells were isolated from cadaveric human donors. Magnetic-activated cell sorting with anti-human CD31 was performed for choroidal endothelial cell isolation. Isolated choroidal endothelial cell cultures had a cobblestone appearance in monolayer cultures and stained positive for the cell-cell adhesion glycoprotein cadherin 5 (vascular endothelial cadherin). Moreover, on 3D Matrigel matrix these cells were able to form capillary-like structures, characteristic of in vitro endothelial cell function. Primary cultures of purified choroidal endothelial cells treated with intermittent administration of 10-7 M cortisol were analysed for the effect on both direct and downstream putative corticosteroid responsive genes (FKBP5, PER1, GILZ1, and SGK1).

Results : We found that intermittent administration of 10-7 M cortisol (mimicking the in vivo situation with diurnal rhythm in blood cortisol levels) led to significant transcriptional upregulation of validated cortisol target genes. Further pharmacological analysis identified the glucocorticoid receptor rather than the mineralocorticoid receptor as the mediator of the cortisol effect on gene expression.

Conclusions : With this optimized choroidal endothelial cell isolation and culturing protocol, we have established an in vitro model that appears very suitable for research on both central serous chorioretinopathy and other diseases in which corticosteroids and choroidal endothelial cells are involved.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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