Induction of endoplasmic reticulum stress in retinal pericytes by glucose deprivation

Kengo Ikesugi, Michael L. Mulhern, Christian J. Madson, Ken Ichi Hosoya, Tetsuya Terasaki, Peter F. Kador, Toshimichi Shinohara

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Diabetic retinopathy is one of the major microvascular complications associated with diabetes mellitus, and the selective degeneration of retinal capillary pericytes is considered to be a hallmark of early retinopathy. Because glucose fluctuations commonly occur in diabetes, we hypothesized that these fluctuations will increase the endoplasmic reticulum (ER) stress and induce the unfolded protein response (UPR) in retinal pericytes. To study whether ER stress and the UPR can be induced in retinal pericytes, rat retinal capillary pericytes were cultured in different concentrations of glucose. Hypoglycemia but not hyperglycemia was found to activate UPR-specific enzymes in pericytes. Strong UPR activation leading to apoptosis was also observed when pericytes were cultured in glucose concentrations that were reduced from high to low or no glucose. These results indicate that induction of UPR is related not only to absolute concentrations but also to a shifting from higher to lower concentrations of glucose.

Original languageEnglish (US)
Pages (from-to)947-953
Number of pages7
JournalCurrent Eye Research
Issue number11
StatePublished - Nov 1 2006


  • Apoptosis
  • Diabetic retinopathy
  • Endoplasmic reticulum (ER) stress
  • Retinal pericytes
  • Unfolded protein response (UPR)

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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