Development of diabetes-induced acidosis in the rat retina.
Development of diabetes-induced acidosis in the rat retina.
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DOI：
10.1016/j.exer.2016.05.028
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发表时间：
2016-08
影响因子：
3.4
通讯作者：
Linsenmeier RA
中科院分区：
文献类型：
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作者：
Dmitriev AV;Henderson D;Linsenmeier RA
我们假设糖尿病动物的视网膜由于糖酵解代谢增加而异常酸性。肿瘤和孤立视网膜中的酸中毒已被证明会导致 VEGF 增加。为了检验这一假设，我们使用离子选择性电极测量了对照大鼠和糖尿病暗适应完整 Long-Evans 大鼠视网膜中细胞外 H+ 浓度（H+ 分布）的经视网膜分布。腹腔注射链脲佐菌素诱发糖尿病。完整的大鼠视网膜通常比血液酸性更强，外核层 (ONL) 中的 [H+]o 峰值平均比脉络膜中的 H+ 高 30 nM。糖尿病动物的轮廓形状相似，但糖尿病 5 周后，糖尿病视网膜开始变得更加酸性。在 1 至 3 个月的糖尿病患者的视网膜中，ONL 和脉络膜之间的差异几乎是对照组的两倍。后来，长达 6 个月的时间里，一些糖尿病患者仍然表现出异常高水平的 [H+]o，但其他患者的酸性甚至低于对照组，因此酸中毒的平均水平没有差异。 H+图谱的较大变异性（动物之间和一只动物记录的图谱之间）将糖尿病视网膜与对照组区分开来。在动物体内，这种变异性不是随机的，而是表现出较高和较低 H+ 的区域。我们得出的结论是，大鼠糖尿病早期（1 至 3 个月）就开始出现视网膜酸中毒。但病情并没有进展，到后期（3～6个月）糖尿病大鼠视网膜的酸度逐渐减少。糖尿病引起的酸中毒也具有强烈的局部特征。因此，糖尿病患者视网膜的 [H+] 分布变异性比对照组大得多。 pH 值影响代谢和神经过程，这些结果表明局部酸中毒可能在糖尿病视网膜病变的发病机制中发挥作用。
We hypothesized that the retina of diabetic animals would be unusually acidic due to increased glycolytic metabolism. Acidosis in tumors and isolated retina has been shown to lead to increased VEGF. To test the hypothesis we have measured the transretinal distribution of extracellular H+ concentration (H+-profiles) in retinae of control and diabetic dark-adapted intact Long-Evans rats with ion-selective electrodes. Diabetes was induced by intraperitoneal injection of streptozotocin. Intact rat retinae are normally more acidic than blood with peak of [H+]o in the outer nuclear layer (ONL) that averages 30 nM higher than H+ in the choroid. Profiles in diabetic animals were similar in shape, but diabetic retinae began to be considerably more acidic after 5 weeks of diabetes. In retinae of 1 to 3 month diabetics the difference between the ONL and choroid was almost twice as great as in controls. At later times, up to 6 months, some diabetics still demonstrated abnormally high levels of [H+]o, but others were even less acidic than controls, so that the average level of acidosis was not different. Greater variability in H+-profiles (both between animals and between profiles recorded in one animal) distinguished the diabetic retinae from controls. Within animals, this variability was not random, but exhibited regions of higher and lower H+. We conclude that retinal acidosis begins to develop at an early stage of diabetes (1 to 3 months) in rats. However, it does not progress, and the acidity of diabetic rat retina was diminished at later stages (3 to 6 months). Also the diabetes-induced acidosis has a strongly expressed local character. As result, the diabetic retinas show much wider variability in [H+] distribution than controls. pH influences metabolic and neural processes, and these results suggest that local acidosis could play a role in the pathogenesis of diabetic retinopathy.