Temporal development of retinal arteriolar endothelial dysfunction in porcine type 1 diabetes
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 eva...
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| Published in: | Investigative ophthalmology & visual science Vol. 53; no. 13; pp. 7943 - 7949 |
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| Main Authors: | , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
The Association for Research in Vision and Ophthalmology
03-12-2012
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | 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.
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.
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.
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. |
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| Bibliography: | Current affiliation: *Central Texas Veterans Health Care System, Temple, Texas. |
| ISSN: | 1552-5783 0146-0404 1552-5783 |
| DOI: | 10.1167/iovs.12-11005 |