Department of Molecular and Cellular Physiology, Louisiana State University, Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
Exp Eye Res. 2010 Mar;90(3):405-12. doi: 10.1016/j.exer.2009.12.002. Epub 2009 Dec 11.
Decreases in retinal blood flow in diabetics could render the retina hypoxic. In mouse and rat models of diabetes, a decrease in retinal blood flow occurs early, within 3-4 weeks of the induction of hyperglycemia, although information is scarce on whether this early decrease in flow induces hypoxia. The purpose of the current study was to determine whether hypoxia-inducible factor (HIF) levels increase following 4 and/or 12 weeks of hyperglycemia in streptozotocin (STZ)-injected mouse (C57BL/6) and rat (Wistar) retinas. Additionally, retinal tissue hypoxia was measured with pimonidazole following 12 weeks of hyperglycemia. These aims were accomplished via immunostaining of cross-sections from enucleated eyes. In mice, staining for HIF-1alpha and HIF-2alpha showed a contrasting pattern, with HIF-1alpha higher in the inner retina than outer, but HIF-2alpha higher in the outer retina than inner. However, in rats, staining for both HIF-1alpha and HIF-2alpha was more intense in the inner retina. The HIF-1alpha staining intensities and patterns were similar between diabetic animals and their non-diabetic counterparts following 4 and 12 weeks of hyperglycemia. The same was true for HIF-2alpha except for a trend toward an increase following 12 weeks of hyperglycemia in mice. Pimonidazole staining showed significant decreases throughout all layers of the central retina and most layers of the peripheral retina of rats (but not mice), following 12 weeks of hyperglycemia. In summary, despite early decreases in flow in rats and mice, retinal HIF-1alpha and HIF-2alpha were not found to be increased, and the extent of hypoxia may even decrease after 12 weeks of hyperglycemia in rats.
糖尿病患者的视网膜血流量减少可能会导致视网膜缺氧。在糖尿病的小鼠和大鼠模型中，尽管关于这种早期血流减少是否会引起缺氧的信息很少，但视网膜血流量在高血糖诱导后 3-4 周内就会早期减少。本研究的目的是确定链脲佐菌素（STZ）注射的小鼠（C57BL/6）和大鼠（Wistar）视网膜中，高血糖症 4 和/或 12 周后，缺氧诱导因子（HIF）水平是否会增加。此外，还通过 12 周高血糖后吡莫硝唑测量视网膜组织缺氧。这些目标是通过对眼球切除后的横截面进行免疫染色来实现的。在小鼠中，HIF-1alpha 和 HIF-2alpha 的染色显示出相反的模式，HIF-1alpha 在视网膜内层的含量高于外层，但 HIF-2alpha 在视网膜外层的含量高于内层。然而，在大鼠中，两种 HIF-1alpha 和 HIF-2alpha 的染色在内层视网膜中更为强烈。在高血糖症 4 和 12 周后，糖尿病动物和非糖尿病动物的 HIF-1alpha 染色强度和模式相似。HIF-2alpha 也是如此，除了在高血糖症 12 周后小鼠有增加的趋势。吡莫硝唑染色显示，在高血糖症 12 周后，大鼠中央视网膜的所有层和周边视网膜的大多数层都出现了显著的缺氧减少。（但不是在小鼠中）。总之，尽管在大鼠和小鼠中早期出现了血流减少，但并未发现视网膜 HIF-1alpha 和 HIF-2alpha 增加，并且在大鼠中，高血糖症 12 周后缺氧的程度甚至可能会降低。
