Temporal development of retinal arteriolar endothelial dysfunction in porcine type 1 diabetes. Academic Article uri icon


  • PURPOSE: Although hyperglycemia is implicated in retinal vascular dysfunction associated with the development of diabetic retinopathy, the temporal influence of hyperglycemia on retinal arteriolar reactivity remains unclear. Development of a large animal model of diabetes relevant to the human retina for evaluation of vascular function is also lacking. Herein, we examined nitric oxide (NO)-mediated dilation and endothelin-1 (ET-1)-induced constriction in retinal arterioles at various time periods in a porcine model of type 1 diabetes. METHODS: Retinal arterioles were isolated from streptozocin-induced diabetic pigs (2, 6, and 12 weeks of hyperglycemia, 427 23 mg/dL) and age-matched control pigs (73 4 mg/dL), and then cannulated and pressurized for vasoreactivity study using videomicroscopic techniques. RESULTS: Retinal arterioles isolated from control and diabetic pigs developed comparable levels of myogenic tone. The endothelium-dependent NO-mediated vasodilations to bradykinin and stepwise increases in luminal flow were significantly reduced within 2 weeks of hyperglycemia. The inhibitory effect was comparable following 6 and 12 weeks of hyperglycemia. However, the endothelium-independent vasodilation to sodium nitroprusside was unaffected. Constriction of retinal arterioles to ET-1 was unaltered at all time periods of hyperglycemia. CONCLUSIONS: Our findings provide the first direct evidence for selective impairment of endothelium-dependent NO-mediated dilation of retinal arterioles within 2 weeks of hyperglycemia in a pig model of diabetes. By contrast, the ability of arteriolar smooth muscle to dilate to NO donor or contract to ET-1 was unaffected throughout the study period. This endothelial vasodilator dysfunction during early diabetes may contribute to development of retinopathy with chronic hyperglycemia.

published proceedings

  • Invest Ophthalmol Vis Sci

altmetric score

  • 0.5

author list (cited authors)

  • Hein, T. W., Potts, L. B., Xu, W., Yuen, J. Z., & Kuo, L.

citation count

  • 27

complete list of authors

  • Hein, Travis W||Potts, Luke B||Xu, Wenjuan||Yuen, Josh Z||Kuo, Lih

publication date

  • January 2012