Attenuation of diabetes-induced retinal vasoconstriction by a thromboxane receptor antagonist

William S Wright1, Jodine E Messina, Norman R Harris

  • 1Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. wwrigh@lsuhsc.edu

Experimental Eye Research
|November 11, 2008
PubMed

Insights

Diabetic mice experienced reduced retinal blood flow, but treatment with vapiprost, a thromboxane receptor antagonist, prevented this decrease. This suggests a key role for thromboxane in diabetic retinal vascular dysfunction.

Area of Science:

  • Ophthalmology
  • Diabetology
  • Pharmacology

Background:

  • Diabetic retinopathy is a leading cause of vision loss.
  • Early diabetes is associated with reduced retinal blood flow in humans and animal models.
  • The role of thromboxane receptor activation in this reduction is not fully understood.

Purpose of the Study:

  • To investigate the role of thromboxane receptor binding in the decrease of retinal blood flow in a mouse model of diabetes.
  • To determine if a selective thromboxane receptor antagonist can prevent or reverse diabetes-induced reductions in retinal blood flow.

Main Methods:

  • Streptozotocin (STZ) induced diabetes in C57BL/6 mice.
  • Mice were treated with the thromboxane receptor antagonist GR32191B (vapiprost) orally for three weeks or via acute injection.
  • Retinal arteriolar and venular diameters and red blood cell (RBC) velocities were measured to calculate retinal blood flow.

Main Results:

  • STZ-induced diabetes resulted in a ~30% decrease in retinal blood flow due to reduced vascular diameters and RBC velocities.
  • Chronic three-week treatment with vapiprost prevented these STZ-induced decreases in retinal blood flow.
  • Acute administration of 1mg/kg vapiprost, but not 0.1mg/kg, induced arteriolar vasodilation in diabetic mice.

Conclusions:

  • Thromboxane receptor activation contributes to the reduction in retinal blood flow observed in diabetes.
  • The thromboxane receptor antagonist vapiprost can attenuate STZ-induced decreases in retinal blood flow.
  • Targeting the thromboxane receptor may be a therapeutic strategy for diabetic retinopathy.

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