Endoplasmic reticulum stress is implicated in retinal inflammation and diabetic retinopathy

FEBS Lett. 2009 May 6;583(9):1521-7. doi: 10.1016/j.febslet.2009.04.007. Epub 2009 Apr 11.

Abstract

Diabetic retinopathy is a chronic low-grade inflammatory disease; however, the mechanisms remain elusive. In the present study, we demonstrated that endoplasmic reticulum (ER) stress was activated in the retina in animal models of diabetes and oxygen-induced retinopathy (OIR). Induction of ER stress by tunicamycin resulted in significantly increased expression of inflammatory molecules in the retina. Inhibition of ER stress by chemical chaperone 4-phenyl butyric acid ameliorated inflammation in cultured human retinal endothelial cells exposed to hypoxia, and in the retinas of diabetic and OIR mice. These findings indicate that ER stress is a potential mediator of retinal inflammation in diabetic retinopathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cells, Cultured
  • DNA Primers
  • Diabetic Retinopathy / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum Chaperone BiP
  • Endoribonucleases / metabolism
  • Eukaryotic Initiation Factor-2 / metabolism
  • Heat-Shock Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Molecular Chaperones / metabolism
  • Oxidative Stress* / drug effects
  • Phenylbutyrates / pharmacology
  • Protein Serine-Threonine Kinases / metabolism
  • Retina / metabolism
  • Retinitis / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / metabolism
  • Tunicamycin / pharmacology
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • DNA Primers
  • Endoplasmic Reticulum Chaperone BiP
  • Eukaryotic Initiation Factor-2
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Phenylbutyrates
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Tunicamycin
  • 4-phenylbutyric acid
  • Ern1 protein, mouse
  • Protein Serine-Threonine Kinases
  • Endoribonucleases