Kumagai A K, Glasgow B J, Pardridge W M
Department of Medicine, UCLA School of Medicine 90024.
Invest Ophthalmol Vis Sci. 1994 May;35(6):2887-94.
The GLUT1 glucose transporter is expressed in endothelial and epithelial barriers, including the retinal capillary endothelium and the retinal pigment epithelium (RPE) of the eye. The present studies were undertaken to determine whether GLUT1 is expressed in additional cell types within the human eye and whether retinal endothelial GLUT1 is aberrantly expressed in diabetic proliferative retinopathy in humans.
Immunohistochemical staining of sections of human eyes obtained at surgery or autopsy from patients with and without diabetes was performed with polyclonal antisera directed against the human GLUT1 glucose transporter.
In the course of this study, an unexpected multicellular localization of GLUT1 in different cellular barriers of the human eye was observed. In the nondiabetic eye, specific staining for GLUT1 was seen in the nerve fiber layer, the ganglion and photoreceptor cell bodies, the capillaries and the RPE of the retina, the basal infoldings of the pigmented and nonpigmented layers of the ciliary body, the capillary endothelium and posterior epithelium of the iris, the corneal epithelium and endothelium, and the endothelium lining of the canal of Schlemm. Müller cells, a type of retinal glial cell identified by morphology and by parallel staining for glial fibrillary acidic protein, also stained intensely positive for GLUT1. The pattern of GLUT1 immunoreactivity in the diabetic eyes was virtually identical to that in the nondiabetic specimens, with the notable exception that the neovascular endothelium of proliferative retinopathy did not stain for GLUT1.
These studies describe the heretofore unrecognized expression of immunoreactive GLUT1 in the ganglion cell layer of the retina, the endothelium lining the canal of Schlemm, the corneal endothelium, and the basal cells of the corneal epithelium of the human eye. The present study also provides evidence for immunoreactive GLUT1 in glial cells of the central nervous system. Because the expression of GLUT1 is characteristic of tissues that possess a barrier function, the absence of GLUT1 immunoreactivity in the neovascular tissue of proliferative diabetic retinopathy suggests that the loss of selective permeability is associated with an absence of facilitated glucose transport in this disorder.
葡萄糖转运蛋白1(GLUT1)在内皮和上皮屏障中表达,包括眼部的视网膜毛细血管内皮和视网膜色素上皮(RPE)。本研究旨在确定GLUT1是否在人眼内的其他细胞类型中表达,以及视网膜内皮GLUT1在人类糖尿病增殖性视网膜病变中是否异常表达。
用针对人GLUT1葡萄糖转运蛋白的多克隆抗血清对手术或尸检获得的有或无糖尿病患者的人眼切片进行免疫组织化学染色。
在本研究过程中,观察到GLUT1在人眼不同细胞屏障中的意外多细胞定位。在非糖尿病眼中,在神经纤维层、神经节和光感受器细胞体、视网膜的毛细血管和RPE、睫状体色素层和非色素层的基底褶、虹膜的毛细血管内皮和后上皮、角膜上皮和内皮以及小梁网的内皮衬里中可见GLUT1的特异性染色。通过形态学和胶质纤维酸性蛋白平行染色鉴定的一种视网膜神经胶质细胞——穆勒细胞,也对GLUT1呈强阳性染色。糖尿病眼中GLUT1免疫反应性模式与非糖尿病标本中的模式几乎相同,值得注意的例外是增殖性视网膜病变的新生血管内皮未对GLUT1染色。
这些研究描述了免疫反应性GLUT1在人眼视网膜神经节细胞层、小梁网内皮、角膜内皮和角膜上皮基底细胞中迄今未被认识的表达。本研究还为中枢神经系统神经胶质细胞中的免疫反应性GLUT1提供了证据。由于GLUT1的表达是具有屏障功能组织的特征,增殖性糖尿病视网膜病变新生血管组织中缺乏GLUT1免疫反应性表明,在这种疾病中选择性通透性的丧失与易化葡萄糖转运的缺乏有关。