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Oxygen Distribution and Consumption in the Normal and Diabetic Rat Retina, and Gene Expression Changes in the Diabetic Rat Retina.

机译：正常和糖尿病大鼠视网膜中的氧分布和消耗，以及糖尿病大鼠视网膜中的基因表达变化。

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摘要

The purpose of these studies was to correlate physiological changes in oxygen distribution and consumption to gene expression changes in the diabetic rat retina. First, techniques to measure PO2 in light- and dark-adapted normal rat retina were established. PO2 depth profiles were recorded from retinas of anesthetized Long-Evans rats using oxygen microelectrodes. The three-layer one-dimensional diffusion model previously used for cat retina was fitted to profiles to determine photoreceptor oxygen consumption per unit volume, Qav. Light adaptation reduced Qav to 60.2+/-4.1% of the dark-adapted value. Minimum PO2 in the outer retina occurred at photoreceptor inner segments in dark adaptation (17.4+/-3.0 mmHg), and light adaptation increased minimum PO2 (29.9+/-5.3 mmHg). As expected, light adaptation increased minimum PO2 and decreased Qav in rat retina, as compared to dark adaptation, by a similar magnitude as in cat retina. However, the dark-adapted minimum PO2 in the outer retina was higher in rat than in cat.;Techniques established in the first study were then applied to investigate PO2 and Qav in the rat retina at 4 and 12 weeks after induction of diabetes. After 4 weeks, diabetic rats had comparable choroidal PO2, Qav, and average inner retinal PO2 to control rats. The 12-week diabetic rats showed no significant change in choroidal PO2 or Qav compared to age-matched controls. However, at 12 weeks, average inner retinal PO2 was significantly lower in controls than in diabetic rats, which was opposite to what was expected. Intraretinal PO2 reflects a balance between oxygen supply and consumption, both of which may change in diabetes.;Finally, qRT-PCR was used to measure gene expression changes in 4- and 12-week diabetic rat retinas. After 12 weeks of diabetes, genes expressed by retinal ganglion cells, including ionotropic glutamate receptor subunits, had significantly reduced mRNA levels, suggesting these cells were lost. Ganglion cell loss may explain why PO2 in the inner retina was higher in diabetic rats. Diabetes did not affect VEGF mRNA expression in the retina at these time points, but diabetes did increase VEGF protein levels. In summary, these studies showed that diabetes affects neural retina, retinal microvasculature, and retinal oxygenation.
机译：这些研究的目的是将氧分布和消耗的生理变化与糖尿病大鼠视网膜中的基因表达变化相关联。首先，建立了用于在适应明暗适应的正常大鼠视网膜中测量PO2的技术。使用氧气微电极从麻醉的Long-Evans大鼠视网膜记录PO2深度分布。将先前用于猫视网膜的三层一维扩散模型拟合到轮廓上，以确定每单位体积Qav的感光器耗氧量。光适应使Qav降低至暗适应值的60.2 +/- 4.1％。在黑暗适应（17.4 +/- 3.0 mmHg）中，视网膜的最小PO2发生在感光器内部段，而光照适应增加了最小PO2（29.9 +/- 5.3 mmHg）。如预期的那样，与黑暗适应相比，光适应增加了大鼠视网膜的最低PO2并降低了Qav，幅度与猫视网膜相似。然而，暗适应的大鼠外视网膜的最低PO2高于猫。大鼠在诱导糖尿病后4周和12周，采用了第一项研究中建立的技术来研究大鼠视网膜中的PO2和Qav。 4周后，糖尿病大鼠的脉络膜PO2，Qav和平均内部视网膜PO2与对照组的大鼠相当。与年龄相匹配的对照组相比，这只12周的糖尿病大鼠的脉络膜PO2或Qav没有明显变化。但是，在第12周，对照组的平均内部视网膜PO2明显低于糖尿病大鼠，这与预期的相反。视网膜内PO2反映了供氧和供氧之间的平衡，这两者在糖尿病中可能会发生变化。最后，qRT-PCR用于测量4周和12周糖尿病大鼠视网膜中的基因表达变化。糖尿病12周后，视网膜神经节细胞表达的基因（包括离子型谷氨酸受体亚基）的mRNA水平明显降低，表明这些细胞丢失了。神经节细胞的丢失可能解释了为什么糖尿病大鼠内视网膜的PO2更高。在这些时间点，糖尿病并未影响视网膜中VEGF mRNA的表达，但糖尿病确实增加了VEGF蛋白的水平。总之，这些研究表明糖尿病会影响神经视网膜，视网膜微脉管系统和视网膜氧合。

著录项

  • 作者

    Lau, Jennifer Chung Min.;

  • 作者单位

    Northwestern University.;

  • 授予单位 Northwestern University.;
  • 学科 Health Sciences Ophthalmology.;Engineering Chemical.;Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2011
  • 页码 167 p.
  • 总页数 167
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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