Purchase this article with an account.
T. W. Hein, Z. Yuan, W. Xu, Y. Ren, L. Kuo; Temporal Development of Retinal Arteriolar Endothelial Dysfunction in Early Stages of Diabetes in Porcine Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):388.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Hyperglycemia and oxidative stress are implicated in retinal vascular dysfunction associated with the development of diabetic retinopathy. Although retinal arterioles provide a major site of flow regulation, the temporal influence of hyperglycemia on retinal arteriolar reactivity and vascular oxidant production remains unclear. The development of a large animal model of diabetes relevant to the human retina for evaluation of vascular function is also lacking. Herein, we examined endothelium-dependent nitric oxide (NO)-mediated dilation and production of superoxide in retinal arterioles at various time points in a porcine model of type 1 diabetes.
Retinal arterioles (<100 µm) were isolated from streptozotocin-induced diabetic pigs (2, 6, 10 and 14 weeks of hyperglycemia, 477±43 mg/dL) and age-matched control pigs (63±14 mg/dL), and then cannulated and pressurized for in vitro study. Vascular diameter changes and superoxide production were monitored using videomicroscopic and dihydroethidium (DHE) staining techniques, respectively.
Dilation of control retinal arterioles to bradykinin but not sodium nitroprusside (SNP) was nearly abolished by endothelial denudation or by NO synthase inhibitor L-NAME. In diabetic retinal arterioles, vasodilation to bradykinin but not to SNP was significantly reduced in a time-dependent manner with threshold and peak impairment at 2 and 6 wk of hyperglycemia, respectively. The inhibitory effect was similar at 6-, 10- and 14-wk periods. DHE staining showed that superoxide levels were markedly increased in endothelium of diabetic arterioles at all time points.
Hyperglycemia selectively impairs endothelium-dependent NO-mediated dilation of retinal arterioles in a time-dependent manner in a diabetic pig model. It is likely that enhanced production of superoxide in retinal arterioles contributes to the initiation and progression of vascular dysfunction by reducing NO bioavailablity. Future studies will elucidate the link between superoxide and endothelial dysfunction in early stages of diabetes.
This PDF is available to Subscribers Only