Department of Ophthalmology, Aarhus University Hospital, DK-8000, Aarhus C, Denmark.
Department of Biomedicine (physiology), University of Aarhus, DK-8000, Aarhus C, Denmark.
Exp Eye Res. 2019 Feb;179:150-156. doi: 10.1016/j.exer.2018.11.006. Epub 2018 Nov 10.
Diabetic retinopathy is characterized by retinal lesions related to disturbances in retinal blood flow. The metabolic dysregulation in diabetes involves hyperglycemia which in both clinical and experimental studies has been shown to induce dilatation of larger retinal vessels, which has been suggested to be mediated by nitric oxide (NO). However, the effects of glucose on the diameter of smaller retinal vessels that are the site of development of diabetic retinopathy are unknown. Diameter changes in porcine retinal arterioles, pre-capillary arterioles and capillaries were studied ex vivo during acute changes in intraluminal glucose concentrations that mimicked changes in plasma glucose in diabetic patients. The experiments were repeated during blocking of NO-synthesis. Intravascular application of 2 mM glucose dilated arterioles and capillaries significantly, while 20 mM glucose dilated precapillary arterioles significantly. Intravascular application of 20 mM glucose dilated precapillary arterioles previously exposed to 2 mM glucose, while no significant diameter changes were observed after application of 2 mM glucose in vessels previously exposed to 20 mM glucose. No diameter changes were observed after application of 5.5 mM glucose in vessels previously exposed to both 2 mM and 20 mM glucose in either order. There was no significant difference between the diameter responses in the absence and presence of NO-synthesis blocker. Glucose induced dilatation of porcine precapillary arterioles ex vivo differs from the response in larger arterioles and capillaries, and the response is unaffected by the blocking of NO-synthesis. This may have implications for understanding the pathophysiology of diseases in the retinal microcirculation, such as diabetic retinopathy.
糖尿病性视网膜病变的特征是与视网膜血流紊乱相关的视网膜病变。糖尿病中的代谢失调涉及高血糖，在临床和实验研究中已表明高血糖会引起较大视网膜血管扩张，这被认为是由一氧化氮 (NO) 介导的。然而，葡萄糖对糖尿病性视网膜病变发生部位的较小视网膜血管直径的影响尚不清楚。在模拟糖尿病患者血浆葡萄糖变化的腔内葡萄糖浓度急性变化期间，研究了离体猪视网膜小动脉、前毛细血管小动脉和毛细血管的直径变化。在阻断 NO 合成的情况下重复了实验。腔内应用 2 mM 葡萄糖显著扩张了小动脉和毛细血管，而 20 mM 葡萄糖显著扩张了前毛细血管小动脉。腔内应用 20 mM 葡萄糖扩张了先前暴露于 2 mM 葡萄糖的前毛细血管小动脉，而在前毛细血管小动脉先前暴露于 20 mM 葡萄糖的情况下，应用 2 mM 葡萄糖后未观察到显著的直径变化。在前毛细血管小动脉先前暴露于 2 mM 和 20 mM 葡萄糖的情况下，应用 5.5 mM 葡萄糖后未观察到直径变化。在不存在和存在 NO 合成抑制剂的情况下，直径反应之间没有显著差异。离体猪前毛细血管小动脉的葡萄糖诱导扩张与较大的动脉和毛细血管的反应不同，并且阻断 NO 合成对其反应没有影响。这可能对理解视网膜微循环中疾病的病理生理学（如糖尿病性视网膜病变）具有重要意义。
