在糖尿病中，相比于其他组织，细胞间黏附分子-1（ICAM-1）在血管内皮细胞的管腔面的诱导程度更大。
ICAM-1 on the luminal surface of endothelial cells is induced to a greater extent in mouse retina than in other tissues in diabetes.
机构信息
Center for Translational Vision Research, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA, USA.
Department of Biology, Case Western Reserve University, Cleveland, OH, USA.
出版信息
Diabetologia. 2022 Oct;65(10):1734-1744. doi: 10.1007/s00125-022-05719-0. Epub 2022 Jul 19.
AIMS/HYPOTHESIS: Induction of intercellular adhesion molecule-1 (ICAM-1) has been implicated in the development of macrovascular and microvascular diseases such as diabetic retinopathy. Lesions of diabetic retinopathy are unique to the retina but the reason for this is unclear, as all tissues are exposed to the same hyperglycaemic insult. We tested whether diabetes induces ICAM-1 on the luminal surface of endothelial cells to a greater extent in the retina than in other tissues and the role of vision itself in that induction.
METHODS
Experimental diabetes was induced in C57Bl/6J, P23H opsin mutant and Gnat1 × Gnat2 double knockout mice using streptozotocin. The relative abundance of ICAM-1 on the luminal surface of endothelial cells in retina and other tissues was determined by conjugating anti-ICAM-1 antibodies to fluorescent microspheres (2 μm), injecting them intravenously and allowing them to circulate for 30 min. After transcardial perfusion, quantification of microspheres adherent to the endothelium in tissues throughout the body was carried out by fluorescent microscopy or flow cytometry. Mice injected with lipopolysaccharide (LPS) were used as positive controls. The difference in leucostasis between retinal and non-retinal vasculature was evaluated.
RESULTS
Diabetes significantly increased ICAM-1-mediated adherence of microspheres to retinal microvessels by almost threefold, independent of sex. In contrast, diabetes had a much smaller effect on endothelial ICAM-1 in other tissues, and more tissues showed a significant induction of endothelial ICAM-1 with LPS than with diabetes. The diabetes-induced increase in endothelial ICAM-1 in retinal vasculature was inhibited by blocking phototransduction in photoreceptor cells. Diabetes significantly increased leucostasis in the retina by threefold compared with a non-ocular tissue (cremaster).
CONCLUSIONS/INTERPRETATION: The diabetes-induced upregulation of ICAM-1 on the luminal surface of the vascular endothelium varies considerably among tissues and is highest in the retina. Induction of ICAM-1 on retinal vascular endothelial cells in diabetes is influenced by vision-related processes in photoreceptor cells. The unique presence of photoreceptors in the retina might contribute to the greater susceptibility of this tissue to vascular disease in diabetes.
目的/假设：细胞间黏附分子-1（ICAM-1）的诱导已被牵涉到诸如糖尿病性视网膜病变等大血管和微血管疾病的发展中。糖尿病性视网膜病变的病变是视网膜所特有的，但原因尚不清楚，因为所有组织都受到相同的高血糖损伤。我们测试了糖尿病是否会在视网膜内皮细胞的管腔表面引起比其他组织更大程度的 ICAM-1 诱导，以及视觉本身在该诱导中的作用。
方法
使用链脲佐菌素在 C57Bl/6J、P23H 视蛋白突变体和 Gnat1×Gnat2 双敲除小鼠中诱导实验性糖尿病。通过将抗 ICAM-1 抗体偶联到荧光微球（2μm）上来确定内皮细胞管腔表面上 ICAM-1 的相对丰度，将其静脉内注射并让其循环 30 分钟。心脏灌注后，通过荧光显微镜或流式细胞术对全身组织中附着在内皮细胞上的微球进行定量。用脂多糖（LPS）注射的小鼠作为阳性对照。评估了视网膜和非视网膜血管之间白细胞沉积的差异。
结果
糖尿病显著增加了视网膜微血管中微球与 ICAM-1 介导的附着，增加了近三倍，与性别无关。相比之下，糖尿病对其他组织中内皮细胞的 ICAM-1 影响要小得多，并且与糖尿病相比，用 LPS 诱导的内皮细胞 ICAM-1 更多组织发生了显著诱导。通过阻断光感受器细胞中的光转导，糖尿病诱导的视网膜血管内皮细胞中 ICAM-1 的增加被抑制。与非眼部组织（提睾肌）相比，糖尿病使视网膜中的白细胞沉积增加了三倍。
结论/解释：在不同组织中，糖尿病诱导的血管内皮细胞腔表面上的 ICAM-1 上调差异很大，在视网膜中最高。糖尿病诱导的视网膜血管内皮细胞中 ICAM-1 的诱导受到光感受器细胞中与视觉相关的过程的影响。视网膜中独特存在的光感受器可能导致该组织在糖尿病中更容易发生血管疾病。
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