ICAM-1 on the luminal surface of endothelial cells is induced to a greater extent in mouse retina than in other tissues in diabetes.
ICAM-1 on the luminal surface of endothelial cells is induced to a greater extent in mouse retina than in other tissues in diabetes.
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DOI：
10.1007/s00125-022-05719-0
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发表时间：
2022-10
期刊：
影响因子：
8.2
通讯作者：
Kern, Timothy S.
中科院分区：
文献类型：
--
作者：
Lessieur, Emma M.;Liu, Haitao;Saadane, Aicha;Du, Yunpeng;Kiser, Jianying;Kern, Timothy S.
关键词：
细胞间黏附分子-1(ICAM-1)的诱导与糖尿病视网膜病变等大血管和微血管疾病的发生密切相关。糖尿病视网膜病变是视网膜独有的，但其原因尚不清楚，因为所有组织都暴露在相同的高血糖刺激下。我们测试了糖尿病是否在视网膜中比在其他组织中更大程度地诱导内皮细胞管腔表面的ICAM-1，以及视觉本身在诱导中的作用。用链脲佐菌素诱导C57BL/6J、P23H视蛋白突变型和GNAT1−/−×GNAT2−/−双基因敲除小鼠实验性糖尿病。通过将抗ICAM-1抗体偶联到荧光微球(2μm)上，静脉注射，循环30min，测定视网膜和其他组织中内皮细胞管腔表面ICAM-1的相对丰度。经心脏灌注后，用荧光显微镜或流式细胞仪对贴壁于血管内皮细胞的微球进行定量。以注射内毒素(LPS)的小鼠为阳性对照。评估视网膜血管和非视网膜血管在白细胞稳定方面的差异。糖尿病显著增加ICAM-1介导的微球与视网膜微血管的粘附性，几乎增加了三倍，与性别无关。相比之下，糖尿病对其他组织内皮细胞ICAM-1的影响要小得多，而且更多的组织显示内毒素显著诱导内皮细胞ICAM-1，而不是糖尿病。糖尿病诱导的视网膜血管内皮细胞ICAM-1的增加可通过阻断光感受器细胞的光信号转导而被抑制。与非眼部组织(Cremaster)相比，糖尿病显著增加了视网膜中白细胞的滞留量三倍。糖尿病引起的血管内皮细胞管腔表面ICAM-1的表达在不同组织中差异很大，在视网膜中表达最高。糖尿病视网膜血管内皮细胞ICAM-1的诱导受感光细胞视觉相关过程的影响。视网膜中光感受器的独特存在可能有助于该组织对糖尿病血管疾病的更大易感性。
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. 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 (2μm), 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. 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). 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.
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影响因子：
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