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人类糖尿病患者血视网膜屏障破坏的电子显微镜免疫细胞化学证明及其与视网膜血管内皮和视网膜色素上皮中醛糖还原酶的关联。

Electron microscopic immunocytochemical demonstration of blood-retinal barrier breakdown in human diabetics and its association with aldose reductase in retinal vascular endothelium and retinal pigment epithelium.

作者信息

Vinores S A, Van Niel E, Swerdloff J L, Campochiaro P A

机构信息

Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.

出版信息

Histochem J. 1993 Sep;25(9):648-63. doi: 10.1007/BF00157879.

DOI:10.1007/BF00157879
PMID:8226103
Abstract

Light-microscopic immunohistochemical staining for albumin has been used to localize sites of blood-retinal barrier (BRB) breakdown in ocular disorders, but the mechanism for BRB compromise cannot be resolved at this level. Using eyes up to 2 days post-mortem from normal patients or from patients with diabetic retinopathy, or other disorders known to cause BRB failure, electron-microscopic immunocytochemistry reveals focal breakdown of the inner BRB, comprised of the retinal vascular endothelium (RVE), which appears to be mediated by diffuse permeation of the RVE cells and by vesicular transport. Permeation of the retinal pigmented epithelial (RPE) cells that comprise the outer BRB also occurs, but there is no evidence of opening of tight junctions between RVE or RPE in any of the disorders evaluated. Increased aldose reductase (AR) expression in the RVE and RPE cells of diabetics as well as in the perivascular retinal astrocytes, which interact with RVE cells to establish the inner BRB, suggests that AR activity and the subsequent intracellular accumulation of sorbitol in these cell types may impair the function of the BRB in diabetes.

摘要

白蛋白的光镜免疫组化染色已被用于定位眼部疾病中血视网膜屏障(BRB)破坏的部位,但在此层面上无法解析BRB受损的机制。使用正常患者或糖尿病视网膜病变患者或其他已知会导致BRB功能障碍的疾病患者死后长达2天的眼睛,电子显微镜免疫细胞化学显示由视网膜血管内皮(RVE)组成的内BRB出现局灶性破坏,这似乎是由RVE细胞的弥漫性渗透和囊泡转运介导的。构成外BRB的视网膜色素上皮(RPE)细胞也会发生渗透,但在所评估的任何疾病中,均未发现RVE或RPE之间紧密连接开放的证据。糖尿病患者的RVE和RPE细胞以及与RVE细胞相互作用以建立内BRB的血管周围视网膜星形胶质细胞中醛糖还原酶(AR)表达增加,这表明AR活性以及这些细胞类型中随后山梨醇的细胞内积累可能会损害糖尿病中BRB的功能。

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Electron microscopic immunocytochemical demonstration of blood-retinal barrier breakdown in human diabetics and its association with aldose reductase in retinal vascular endothelium and retinal pigment epithelium.人类糖尿病患者血视网膜屏障破坏的电子显微镜免疫细胞化学证明及其与视网膜血管内皮和视网膜色素上皮中醛糖还原酶的关联。
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2
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本文引用的文献

1
Disruption of blood-retinal barrier in experimental diabetic rats: an electron microscopic study.实验性糖尿病大鼠血视网膜屏障的破坏:一项电子显微镜研究。
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Clinicopathologic study of blood-retinal barrier in experimental diabetes mellitus.实验性糖尿病血视网膜屏障的临床病理研究
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Breakdown of blood. Retinal barrier in RCS rats with inherited retinal degeneration.血液分解。患有遗传性视网膜变性的RCS大鼠的视网膜屏障。
Pathophysiology. 2017 Dec;24(4):229-241. doi: 10.1016/j.pathophys.2017.07.001. Epub 2017 Jul 12.
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Osmotic expression of aldose reductase in retinal pigment epithelial cells: involvement of NFAT5.醛糖还原酶在视网膜色素上皮细胞中的渗透表达:NFAT5的作用。
Graefes Arch Clin Exp Ophthalmol. 2016 Dec;254(12):2387-2400. doi: 10.1007/s00417-016-3492-x. Epub 2016 Sep 14.
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Consumption of polyphenol-rich Morus alba leaves extract attenuates early diabetic retinopathy: the underlying mechanism.富含多酚的桑叶提取物的摄入可减轻早期糖尿病视网膜病变:潜在机制。
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Caspase-14 expression impairs retinal pigment epithelium barrier function: potential role in diabetic macular edema.半胱天冬酶-14的表达损害视网膜色素上皮屏障功能:在糖尿病性黄斑水肿中的潜在作用。
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RPE barrier breakdown in diabetic retinopathy: seeing is believing.糖尿病性视网膜病变中的视网膜色素上皮屏障破坏:眼见为实。
J Ocul Biol Dis Infor. 2011 Jun;4(1-2):83-92. doi: 10.1007/s12177-011-9068-4. Epub 2011 Dec 31.
8
TNFalpha is required for late BRB breakdown in diabetic retinopathy, and its inhibition prevents leukostasis and protects vessels and neurons from apoptosis.TNFalpha 在糖尿病性视网膜病变中晚期 BRB 破裂中起关键作用,其抑制作用可以防止白细胞淤滞,并防止血管和神经元发生细胞凋亡。
Invest Ophthalmol Vis Sci. 2011 Mar 10;52(3):1336-44. doi: 10.1167/iovs.10-5768. Print 2011 Mar.
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Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: a study using quail--chick transplantation chimeras.发育中的神经组织诱导侵入的内皮细胞形成血脑屏障特征:一项使用鹌鹑-小鸡移植嵌合体的研究。
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Micropinocytic ingestion of glycosylated albumin by isolated microvessels: possible role in pathogenesis of diabetic microangiopathy.分离微血管对糖基化白蛋白的微胞饮摄取:在糖尿病微血管病变发病机制中的可能作用。
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Pathologic studies of the blood--retinal barrier in the spontaneously diabetic BB rat.自发性糖尿病BB大鼠血视网膜屏障的病理学研究
Invest Ophthalmol Vis Sci. 1984 Mar;25(3):302-11.
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Galactose-induced retinal capillary basement membrane thickening: prevention by Sorbinil.半乳糖诱导的视网膜毛细血管基底膜增厚:Sorbinil的预防作用
Invest Ophthalmol Vis Sci. 1983 Nov;24(11):1519-24.
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Retinal capillaries: basement membrane thickening by galactosemia prevented with aldose reductase inhibitor.视网膜毛细血管:半乳糖血症所致的基底膜增厚可被醛糖还原酶抑制剂预防。
Science. 1983 Sep 16;221(4616):1177-9. doi: 10.1126/science.6612330.