McLeod D S, Lefer D J, Merges C, Lutty G A
Wilmer Ophthalmologic Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Am J Pathol. 1995 Sep;147(3):642-53.
Elevated expression of intercellular adhesion molecule-1 (ICAM-1) as well as E- and P-selectin occurs on the vascular endothelium in a number of disease states and is thought to play an early critical role in the adhesion of circulating leukocytes to the endothelium. The goal of the present study was to investigate the immunolocalization of these molecules in the retina and choroid of postmortem human tissue sections from nondiabetic and diabetic subjects. Whereas ICAM-1 was localized primarily within the choriocapillaris of nondiabetic subjects, immunoreactivity in diabetics was significantly elevated throughout the choroidal vasculature and within retinal blood vessels (P < 0.05). In the choroid, P-selectin was most prominent in veins of the nondiabetic, whereas in diabetics, P-selectin was significantly elevated in arteries (P < 0.001) and veins (P < 0.05) and, in some cases, was also observed in choriocapillaris. P-selectin immunoreactivity was not observed in the retina of any subject. E-selectin immunoreactivity was not observed in choroid or retina in any subjects. Neutrophil numbers per square millimeter of tissue were significantly elevated in diabetic choroid (P < 0.05) and retina (P < 0.001). Our results demonstrate that ICAM-1 and P-selectin are constitutively expressed in the normal choroid and are upregulated in the choroidal vasculature in diabetes, but only ICAM-1 was upregulated in the retina of diabetic subjects. Increased cell adhesion molecule expression may contribute to the retinal and choroidal microangiopathy observed in diabetics by enhancing leukocyte adhesion and consequently the incidence of capillary obstruction and endothelial cell injury.
在许多疾病状态下,细胞间黏附分子-1(ICAM-1)以及E-选择素和P-选择素在血管内皮细胞上的表达会升高,并且被认为在循环白细胞与内皮细胞的黏附中起早期关键作用。本研究的目的是调查这些分子在非糖尿病和糖尿病受试者死后人体组织切片的视网膜和脉络膜中的免疫定位。在非糖尿病受试者中,ICAM-1主要定位于脉络膜毛细血管内,而在糖尿病患者中,脉络膜血管系统和视网膜血管内的免疫反应性显著升高(P<0.05)。在脉络膜中,P-选择素在非糖尿病患者的静脉中最为突出,而在糖尿病患者中,P-选择素在动脉(P<0.001)和静脉(P<0.05)中显著升高,在某些情况下,在脉络膜毛细血管中也可观察到。在任何受试者的视网膜中均未观察到P-选择素免疫反应性。在任何受试者的脉络膜或视网膜中均未观察到E-选择素免疫反应性。糖尿病脉络膜(P<0.05)和视网膜(P<0.001)每平方毫米组织中的中性粒细胞数量显著升高。我们的结果表明,ICAM-1和P-选择素在正常脉络膜中组成性表达,在糖尿病患者的脉络膜血管系统中上调,但只有ICAM-1在糖尿病受试者的视网膜中上调。细胞黏附分子表达的增加可能通过增强白细胞黏附,进而增加毛细血管阻塞和内皮细胞损伤的发生率,导致糖尿病患者出现视网膜和脉络膜微血管病变。