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Dexamethasone Intravitreal Implant Is Active at the Molecular Level Eight Weeks after Implantation in Experimental Central Retinal Vein Occlusion

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  • Lasse Jørgensen Cehofski, University of Southern Denmark, Aalborg University
  • ,
  • Anders Kruse, Aalborg University
  • ,
  • Mads Odgaard Mæng, Aalborg University, Denmark
  • Benn Falch Sejergaard, Aalborg University
  • ,
  • Anders Schlosser, University of Southern Denmark
  • ,
  • Grith Lykke Sorensen, University of Southern Denmark
  • ,
  • Jakob Grauslund, University of Southern Denmark
  • ,
  • Bent Honoré
  • Henrik Vorum, Aalborg University

Central retinal vein occlusion (CRVO) is a visually disabling condition resulting from a thrombus in the major outflow vessel of the eye. The inflammatory response in CRVO is effectively treated with a dexamethasone (DEX) intravitreal implant. Uncovering the proteome changes following DEX implant intervention in CRVO may identify key proteins that mediate the beneficial effects of DEX. In six Göttingen minipigs, CRVO was induced in both eyes with an argon laser using a well-established experimental model. The right eyes were treated with a DEX intravitreal implant (Ozurdex, Allergan), while the left control eyes received a sham injection. Eight weeks after DEX intervention, retinal samples were collected and analyzed with tandem mass tag-based mass spectrometry. DEX implant intervention resulted in the upregulation of peptidyl-prolyl cis-trans isomerase FKBP5 (FKBP5) and ubiquilin-4. Immunohistochemistry showed expression of FKBP5 in the nuclei in all cellular layers of the retina. Cell adhesion molecule 3, tumor necrosis factor receptor superfamily member 16, and trans-1,2-dihydrobenzene-1,2-diol dehydrogenase were downregulated following DEX intervention. The upregulation of the corticosteroid-sensitive protein FKBP5 suggests that the implant remained active at the molecular level after eight weeks of treatment. Future studies may investigate if FKBP5 regulates the efficacy and duration of the DEX implant.

Original languageEnglish
Article number5687
JournalMolecules (Basel, Switzerland)
Volume27
Issue17
Number of pages8
ISSN1420-3049
DOIs
Publication statusPublished - Sep 2022

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