Expression of intraocular peroxisome proliferator-activated receptor gamma in patients with proliferative diabetic retinopathy

J Diabetes Complications. 2015 Mar;29(2):275-81. doi: 10.1016/j.jdiacomp.2014.10.010. Epub 2014 Oct 29.

Abstract

Aims: To determine whether peroxisome proliferator-activated receptor gamma (PPARγ), which is recognized as a component of the exosomes circulating in plasma, is expressed intraocularly in patients with proliferative diabetic retinopathy (PDR).

Methods: The concentrations of PPARγ and vascular endothelial growth factor (VEGF) in the aqueous humor and vitreous of 50 eyes with PDR and 38 control eyes were determined by ELISA. The levels of the mRNA and protein of PPARγ were determined in proliferative membranes from 12 PDR and 5 control eyes by quantitative RT-PCR and immunohistochemical analyses.

Results: PPARγ was detected in the culture media of human umbilical vein endothelial cells indicating that PPARγ can be released into the extracellular fluid. The PPARγ concentrations in the aqueous humor and vitreous fluid were significantly higher in PDR patients than in controls (P<0.0005). There was a significant positive correlation between the PPARγ and VEGF concentrations (P<0.0005). The level of PPARγ increased as the clinical stage advanced. The expressions of the mRNA and protein of PPARγ were higher in the membranes of PDR than those of controls. Anti-VEGF therapy significantly reduced the VEGF concentration (P<0.0001) but not the PPARγ concentration.

Conclusions: PPARγ may play an important role in the pathogenesis of PDR.

Keywords: Angiogenesis; Diabetic retinopathy; Exosomes; Peroxisome proliferator-activated receptor gamma; Vascular endothelial growth factor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Aqueous Humor / drug effects
  • Aqueous Humor / metabolism*
  • Bevacizumab
  • Cells, Cultured
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Retinopathy / drug therapy
  • Diabetic Retinopathy / metabolism*
  • Diabetic Retinopathy / pathology
  • Diabetic Retinopathy / physiopathology
  • Epiretinal Membrane / metabolism
  • Epiretinal Membrane / pathology
  • Female
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Intravitreal Injections
  • Male
  • Middle Aged
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Severity of Illness Index
  • Up-Regulation* / drug effects
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism
  • Vitreous Body / drug effects
  • Vitreous Body / metabolism*
  • Vitreous Body / pathology

Substances

  • Antibodies, Monoclonal, Humanized
  • PPAR gamma
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab