Hypoxia and the expression of HIF-1alpha and HIF-2alpha in the retina of streptozotocin-injected mice and rats.

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-1α and HIF-2α showed a contrasting pattern, with HIF-1α higher in the inner retina than outer, but HIF-2α higher in the outer retina than inner. However, in rats, staining for both HIF-1α and HIF-2α was more intense in the inner retina. The HIF-1α 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-2α 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-1α and HIF-2α were not found to be increased, and the extent of hypoxia may even decrease after 12 weeks of hyperglycemia in rats.

糖尿病患者视网膜血流减少可能导致视网膜缺氧。在糖尿病小鼠和大鼠模型中，视网膜血流在高血糖诱导后的3 - 4周内早期就会减少，不过关于这种早期血流减少是否会导致缺氧的信息还很少。本研究的目的是确定在注射链脲佐菌素（STZ）的小鼠（C57BL/6）和大鼠（Wistar）视网膜出现高血糖4周和/或12周后，缺氧诱导因子（HIF）水平是否会升高。此外，在高血糖12周后，用吡莫硝唑测量视网膜组织缺氧情况。这些目标是通过对摘除眼球的横截面进行免疫染色来实现的。在小鼠中，HIF - 1α和HIF - 2α的染色呈现出对比模式，HIF - 1α在视网膜内层比外层高，而HIF - 2α在视网膜外层比内层高。然而，在大鼠中，HIF - 1α和HIF - 2α在视网膜内层的染色都更强烈。在高血糖4周和12周后，糖尿病动物和非糖尿病动物之间HIF - 1α的染色强度和模式相似。HIF - 2α也是如此，除了在小鼠高血糖12周后有升高的趋势。吡莫硝唑染色显示，在高血糖12周后，大鼠（而非小鼠）的视网膜中央所有层和周边大部分层都显著减少。总之，尽管大鼠和小鼠早期血流减少，但未发现视网膜HIF - 1α和HIF - 2α升高，而且在大鼠高血糖12周后，缺氧程度甚至可能降低。