Dexamethasone intravitreal implant downregulates PDGFR-α and upregulates caveolin-1 in experimental branch retinal vein occlusion

Lasse Jørgensen Cehofski, Anders Kruse, Sigriður Olga Magnusdottir, Alexander Nørgård Alsing, Jonas Ellegaard Nielsen, Svend Kirkeby, Bent Honoré, Henrik Vorum

Research output: Contribution to journalJournal articleResearchpeer-review

16 Citations (Scopus)

Abstract

A dexamethasone (DEX) intravitreal implant (OZURDEX) provides an effective treatment of inflammation secondary to branch retinal vein occlusion (BRVO). Retinal proteome changes which mediate the beneficial effects of the implant remain poorly understood. To study retinal proteome changes in BRVO following an intervention with a DEX implant this study combined an experimental model of BRVO with proteomic techniques. In eight Danish Landrace pigs experimental BRVO was induced in both eyes using argon laser. After inducing BRVO a DEX implant was injected into the right eye of each animal while the left control eye was given an identical injection without an implant. Fifteen days after BRVO and DEX implant intervention the retinas were excised and analyzed with tandem mass tag based mass spectrometry. A total of 26 significantly changed proteins were identified. DEX intervention reduced the retinal levels of platelet-derived growth factor receptor-α (PDGFR-α) and vascular endothelial growth factor receptor 2 (VEGFR-2). DEX treatment resulted in increased levels of caveolin-1, peptidyl-prolyl cis-trans isomerase FKBP5 and transgelin. Changes in PDGFR-α and caveolin-1 were confirmed with immunohistochemistry. In BRVO treated with the DEX implant a strong reaction for caveolin-1 was observed in the innermost retinal layers. DEX implant intervention may inhibit PDGF signaling by decreasing the retinal level of PDGFR-α while an increased content of caveolin-1 may help maintain the integrity of the blood-retinal barrier.

Original languageEnglish
JournalExperimental Eye Research
Volume171
Pages (from-to)174-182
Number of pages9
ISSN0014-4835
DOIs
Publication statusPublished - Jun 2018

Bibliographical note

Copyright © 2018 Elsevier Ltd. All rights reserved.

Keywords

  • Animals
  • Blood-Retinal Barrier
  • Blotting, Western
  • Caveolin 1/metabolism
  • Chromatography, Liquid
  • Dexamethasone/administration & dosage
  • Disease Models, Animal
  • Down-Regulation
  • Drug Implants
  • Glucocorticoids/administration & dosage
  • Intravitreal Injections
  • Mass Spectrometry
  • Microfilament Proteins/metabolism
  • Muscle Proteins/metabolism
  • Peptidylprolyl Isomerase/metabolism
  • Proteomics
  • Receptor, Platelet-Derived Growth Factor alpha/metabolism
  • Retinal Vein Occlusion/drug therapy
  • Swine
  • Tacrolimus Binding Proteins/metabolism
  • Up-Regulation
  • Vascular Endothelial Growth Factor Receptor-2/metabolism

Fingerprint

Dive into the research topics of 'Dexamethasone intravitreal implant downregulates PDGFR-α and upregulates caveolin-1 in experimental branch retinal vein occlusion'. Together they form a unique fingerprint.

Cite this