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Translocation of H-Ras and its implications in the development of diabetic retinopathy

Renu A Kowluru1, Mamta Kanwar

  • 1Department of Ophthalmology, Kresge Eye Institute, Wayne State University, 4717 St. Antoine, Detroit, MI 48201, USA. rkowluru@med.wayne.edu

Biochemical and Biophysical Research Communications
|July 18, 2009
PubMed

Insights

Diabetic hyperglycemia accelerates retinal capillary cell apoptosis by increasing H-Ras protein translocation to the membrane. Farnesylation inhibitors and H-Ras-siRNA can prevent this process, offering potential therapeutic strategies.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Ophthalmology

Background:

  • Hyperglycemia in diabetes mellitus is linked to retinal capillary cell apoptosis.
  • H-Ras, a G-protein, translocates to the cell membrane after post-translational modification.
  • This translocation is implicated in the pathogenesis of diabetic retinopathy.

Purpose of the Study:

  • To investigate the mechanism of retinal H-Ras activation in diabetes.
  • To determine the role of H-Ras membrane translocation in diabetic-induced retinal apoptosis.
  • To explore potential therapeutic interventions targeting H-Ras.

Main Methods:

  • Quantification of H-Ras and Raf-1 in retinal membrane and cytosol fractions from diabetic rats.
  • Assessment of simvastatin's effect on diabetes-induced alterations in protein translocation.
  • Evaluation of H-Ras-siRNA's impact on membrane translocation and apoptosis in bovine retinal endothelial cells (BRECs).

Main Results:

  • Diabetes increased H-Ras and Raf-1 expression in retinal membranes.
  • Simvastatin inhibited diabetes-induced H-Ras and Raf-1 membrane translocation.
  • Glucose exposure in BRECs increased membrane H-Ras; H-Ras-siRNA reduced this translocation and apoptosis.

Conclusions:

  • Membrane translocation of H-Ras is a key mechanism in accelerated retinal capillary cell apoptosis in diabetes.
  • Targeting H-Ras post-translational modification and translocation may offer a therapeutic approach for diabetic retinopathy.

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