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

Exp Eye Res. 2018 Jun:171:174-182. doi: 10.1016/j.exer.2018.02.029. Epub 2018 Mar 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Retinal Vein Occlusion / metabolism
  • Swine
  • Tacrolimus Binding Proteins / metabolism
  • Up-Regulation
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Caveolin 1
  • Drug Implants
  • Glucocorticoids
  • Microfilament Proteins
  • Muscle Proteins
  • transgelin
  • Dexamethasone
  • Receptor, Platelet-Derived Growth Factor alpha
  • Vascular Endothelial Growth Factor Receptor-2
  • Tacrolimus Binding Proteins
  • Peptidylprolyl Isomerase
  • tacrolimus binding protein 5