糖尿病视网膜病变白细胞和粘附分子的研究进展

糖尿病视网膜病变发病机制复杂，本文综述了粘附分子在糖尿病视网膜病变中表达变化、白细胞特征及在糖尿病视网膜病变始动和发展的潜在作用，干预糖尿病视网膜病变粘附分子异常表达、白细胞聚集的可能性。     

粘附分子在糖尿病视网膜病变的研究进展

糖尿病视网膜病变发病机制复杂,至今未能完全阐明。而粘附分子在糖尿病视网膜病变的发生、发展中起着相当重要的作用,成为近年的研究热点。本文对粘附分子在糖尿病视网膜病变中的作用及对其干预作一综述。     

粘附分子在糖尿病视网膜病变的研究进展

糖尿病视网膜病变发病机制复杂，至今未能完全阐明。而粘附分子在糖尿病视网膜病变的发生、发展中起着相当重要的作用，成为近年的研究热点。本文对粘附分子在糖尿病视网膜病变中的作用及对其干预作一综述。     

血清ICAM-1水平与糖尿病性视网膜病变关系的研究

目的:探讨糖尿病患者血清细胞间粘附分子-1(ICAM-1)的水平变化及临床意义。方法:应用ELISA方法测定53例Ⅱ型糖尿病患者及对照组健康人血清中细胞间粘附分子-1的含量。结果:糖尿病视网膜病变患者血清ICAM-1明显高于对照组;糖尿病视网膜病变患者血清ICAM-1明显高于非糖尿病视网膜病变患者;增殖性糖尿病视网膜病变患者高于非增殖性糖尿病视网膜病变患者。结论:ICAM-1可能在DR发病中起着一定的作用。     

糖尿病视网膜病变发病机制及其药物治疗研究进展

糖尿病视网膜病变是糖尿病的常见并发症,研究其发病机制对糖尿病视网膜病变的防治具有重要意义。视网膜神经细胞的病变与微血管病变相同,是糖尿病视网膜病变的重要组成部分,在糖尿病发病初期即可出现,包括神经元细胞的凋亡、神经胶质细胞的改变、炎性递质的释放及谷氨酸盐的正常代谢受损。由于糖尿病视网膜病变在其发生、发展过程中出现白细胞黏附、聚集和移行,血管渗透性增加和血流动力学改变,多种炎性反应因素的参与及其特征性的病理学改变,越来越多的学者认为糖尿病视网膜病变可能是一种慢性、低度炎性反应。目前对糖尿病视网膜病变发病机制的深入研究,将为有效预防和治疗糖尿病视网膜病变开辟新途径。（中华眼科杂志,2008,44：76-81）     

ICAM-1和VCAM-1在糖尿病视网膜病变中的作用

糖尿病会造成视网膜很多异常改变,其中包括细胞间粘附分子-1(intercellular adhesion molecule-1,ICAM-1)和血管细胞粘附分子-1(vascular cell adhesion molecule-1,VCAM-1)的上调,这显示了炎症反应在糖尿病视网膜病变(diabetic retinopathy,DR)发展中发挥了一些作用。本文针对粘附分子ICAM-1和VCAM-1在DR的血管内皮细胞的损伤及其在炎症反应中发挥的重要作用进行了简要分析。     

炎症在糖尿病视网膜病变发病机制中的作用

糖尿病视网膜病变（DR）是糖尿病常见的严重并发症,也是主要的致盲疾病之一,其发病机制尚不清楚。近年的研究发现早期糖尿病视网膜中白细胞粘附增加,并与DR微血管损伤在时间和空间上一致。同时细胞内粘附分子-1（ICAM-1）及其基因表达上调,抗ICAM-1抗体及CD18抗体可抑制糖尿病引起的白细胞粘附和血管内皮损伤。血管内皮生长因子（VEGF）和糖基化终产物（AGEs）可引起DR中的炎症改变。增加视网膜内VEGF及AGEs可明显增加白细胞粘附和血-视网膜屏障的破坏。非甾体类抗炎药物可能参与抑制糖尿病视网膜炎症。     

粘附分子与糖尿病性视网膜病变的研究

糖尿病性视网膜病变（ＤＲ）是进展性微血管病变，其发病机制尚未完全阐明，但被认为与多种因素的协同作用有关，近年研究表明某些细胞粘附分子如ＩＣＡＭ－１（细胞间粘附分子－１）及Ｉｎｔｅｇｒｉｎ（整合素）与糖尿病性视网膜病变的发生密切相关，且其单克隆抗体的阻断作用可能成为一种有效的治疗途径。本文就有关粘附分子及其在ＤＲ发生的病理机制中的作用作一综述。     

粘附分子与糖尿病性视网膜病变的研究

糖尿病性视网膜病变（ＤＲ）是进展性微血管病变，其发病机制尚未完全阐明，但被认为与多种因素的协同作用有关。近年研究表明某些细胞粘附分子如ＩＣＡＭ－１（细胞间粘附分子－１）及Ｉｎｔｅｇｒｉｎ（整合素）与糖尿病性视网膜病变的发生密切相关，且其单克隆抗体的阻断作用可能成为一种新的治疗途径。本文就有关粘附分子及其在ＤＲ发生的病理机制中的作用作一综述     

12-脂氧化酶与糖尿病视网膜病变的相关性

糖尿病视网膜病变是糖尿病微血管病变的严重眼部并发症,当前研究认为视网膜的炎症损伤在糖尿病视网膜病变早期发挥重要作用.12-脂氧化酶是一种多元不饱和脂肪酸的氧化酶,其最终过氧化产物为12-羟基二十碳四烯酸.研究证明,12-羟基二十碳四烯酸可以上调血管紧张素Ⅱ的水平,参与白细胞淤滞、毛细血管周细胞凋亡,导致慢性氧化应激,影响视网膜新生血管的形成.上述改变均是糖尿病时视网膜发生病理改变的重要环节.本文主要综合近年来国内外研究成果,详述12-脂氧化酶对糖尿病视网膜病变早期微血管病变发生的影响.     

糖尿病视网膜前膜中ICAM-1及Mac-1的免疫组织化学研究

目的 观察增生型糖尿病视网膜病变（ＰＤＲ）的纤维增生视网膜前膜（ＥＲＭ）中粘附分子（ＩＣＡＭ－１,Ｍａｃ－１）的表达。方法 用免疫组织化学方法对９例ＰＤＲ患者行玻璃体切割术时剥离的视网膜前膜进行观察。其中糖尿病视网膜病变Ⅳ期４例,Ⅴ期５例。结果 ＩＣＡＭ－１和Ｍａｃ－１在８例视网膜前膜中表达,表达率８９％,ＩＣＡＭ－１和Ｍａｃ－１阳性表达在糖尿病分型及分期中无明显差别。结论 ＩＣＡＭ－１和Ｍａｃ－１在增生型糖尿病视网膜中表达,糖尿病视网膜病变的发病中有粘附分子参与。     

细胞因子与糖尿病视网膜病变的研究进展

糖尿病视网膜病变（DR）是一种发生进行性视力损害的糖尿病（DM）并发症,其特征是毛细血管闭锁、微循环障碍和局部缺血性视网膜新生血管形成,其确切的发病机制尚不清楚。最近有研究认为DR可能与视网膜毛细血管炎症反应有关。由于细胞因子能引起炎症反应和黏附分子表达,因此细胞因子增加单核细胞和内皮细胞黏附的过程被认为是DR发生发展过程中的关键事件。就血管内皮生长因子（VEGF）、转化生长因子-β（TGF-β）、碱性成纤维细胞生长因子（bFGF）等多种细胞因子在DR中的作用进行综述。     

In vivo evaluation of leukocyte dynamics in the retinal and choroidal circulation

We have developed a new method to visualize leukocytes and evaluate their kinetics in the chorioretinal microcirculation of the living eyes. Nuclear staining dyes and a scanning laser ophthalmoscope were used to image leukocytes in the fundus. Acridine orange was used to visualize leukocytes in the retinal microcirculation. For imaging leukocytes in the choroid, indocyanine green was injected intravenously. Dynamics of leukocytes in the capillaries of the retina and choroid were quantitatively estimated in monkeys and rats. This method also allowed evaluation of leukocyte-endothelial interactions, such as rolling or firm adhesion, in vivo. Acridine orange leukocyte fluography was used to study leukocyte dynamics in the following experimentally induced microcirculatory disturbances of the retina: 1) interferon-associated retinopathy, 2) ischemia-reperfusion injury of the retina, and 3) experimental diabetes mellitus. 1) Interferon-associated retinopathy Systemic administration of interferon alpha enhanced leukocyte-endothelial interactions in the retina, which resulted in leukocyte rolling and entrapment in the retinal capillary beds. Leukocyte accumulation was also detected in the lung. The entrapment or accumulation of leukocytes in the microcirculation was inhibited by simultaneous administration of corticosteroids or other agents. These results suggested that leukocytes play a major role in the development of adverse effects of interferon, such as retinopathy or interstitial pneumonia. 2) Ischemia-reperfusion injury of the retina During reperfusion period after transient (60 min) retinal ischemia by optic nerve ligation, the rolling of leukocytes in the retinal veins was prominent and numerous leukocytes were trapped in the retinal capillaries. The number of rolling leukocytes was at a maximum 12 hours after reperfusion. Leukocyte entrapment peaked at 24 hours after reperfusion. By blocking adhesion molecules on the vascular endothelium, these leukocyte-endothelial interactions were effectively inhibited. Postischemic retinal atrophy was also inhibited by blocking adhesion molecules. These results suggested that leukocytes may be major players in the pathophysiology of ischemia reperfusion injury of the retina. 3) Experimental diabetes mellitus Leukocyte dynamics in the retina were studied in streptozotocin-induced diabetes and spontaneous diabetes (OLETF rats). In both diabetic models, leukocyte entrapment in the retinal capillaries was increased even in the early stages of diabetes. Fluorescein angiography revealed that trapped leukocytes disturbed the regional capillary blood flow in the downstream. Enhanced expression of adhesion molecules was observed in the capillary endothelium of the retina in the diabetic rats. Leukocyte entrapment in the retinal capillaries might cause microvascular occlusions and dysfunction, in turn causing diabetic retinopathy.     

Serum inflammatory markers in diabetic retinopathy

PURPOSE: To evaluate the association of serum factors with the severity of diabetic retinopathy and to assess their presence in retinal tissue obtained at autopsy. METHODS: The following serum factors of 93 subjects were examined at the National Eye Institute (NEI) clinical center: the chemokines regulated on activation, normal T-cell expressed and presumably secreted (RANTES)/CCL5, epithelial neutrophil activator (ENA)-78/CXCL5, interferon-induced protein (IP)-10/CXCL10, stromal cell-derived factor (SDF)-1alpha/CXCLl2, monocyte chemoattractant protein (MCP)-1/CCL2, macrophage inflammatory protein (MIP)-1alpha/CCL3, interleukin (IL)-8/CXCL8; the cytokine IL-6; the cell adhesion molecules intercellular adhesion molecule (ICAM-1/CD54) and vascular cell adhesion molecule (VCAM/CD106); and the growth factor vascular endothelial growth factor (VEGF). Logistic regression was performed to assess the association of these factors with age, sex, severity of retinopathy, hemoglobin A(1C), total cholesterol, creatinine, duration of diabetes, and presence of macular edema. The outcome assessed was severity of retinopathy. Frozen sections of two donor eyes obtained at autopsy from a donor with documented severe nonproliferative diabetic retinopathy and diabetic macular edema and of a normal nondiabetic eye were processed by immunoperoxidase staining with primary antibodies against RANTES, MCP-1, ICAM-1, and LFA-1alpha/CD11a. RESULTS: The levels of RANTES and SDF-1alpha were significantly elevated in patients with at least severe nonproliferative diabetic retinopathy compared with those with less severe diabetic retinopathy (P < 0.001 and 0.007, respectively). Positive immunostaining was observed in the inner retina for MCP-1 and RANTES of the patient with diabetes. Staining was strongly positive throughout the diabetic retina for ICAM-1. Normal retinal tissues showed little reactivity. CONCLUSIONS: Serum chemokines were significantly elevated in patients with at least severe nonproliferative diabetic retinopathy compared with those who had less severe retinopathy. Elevated levels of the chemokines and cell adhesion molecules were also identified in eyes of a donor with ischemic diabetic retinopathy. These findings provide evidence to support the role of inflammation in the pathogenesis of diabetic retinopathy.     

同型半胱氨酸与糖尿病视网膜病变的相关性

同型半胱氨酸（Hcy）是一种与半胱氨酸同系的四碳含硫氨基酸，在细胞内由蛋氨酸代谢脱去甲基后形成，是蛋氨酸代谢的中间产物。近年来，越来越多的研究表明同型半胱氨酸是一种反应性血管损伤氨基酸，具有细胞毒性，与微血管疾病如糖尿病视网膜病变（DR）存在着密切的关系。Hcy可通过氧化应激系统影响血管内皮的功能，促进低密度脂蛋白过氧化，造成细胞结构和功能的破坏，通过诱导多种趋化因子、黏附分子等在体内的表达，而导致微血管疾病的发生。就Hcy与DR发病的相关性及其发病机制的研究现状进行综述。     

Pathogenetic potential of leukocytes in diabetic retinopathy

Recently, increasing interest has been directed toward the role of leukocytes in microvascular disorders including diabetic retinopathy because of their large cell volume, high cytoplasmic rigidity, natural tendency to stick to the vascular endothelium, and capacity to generate toxic superoxide radicals and proteolytic enzymes. Leukocytes in diabetes are reported to be less deformable and more activated, and may be involved in capillary non-perfusion, endothelial cell damage, and vascular leakage in the retinal microcirculation. In fact, histological studies show many capillary occlusions by leukocytes and capillary dropout or degeneration associated with leukocytes in the diabetic retina. Serial acridine orange leukocyte fluorography and fluorescein angiography studies also identify trapped leukocytes directly associated with areas of downstream non-perfusion in the diabetic retinal microcirculation. More recent studies suggest that adhesion molecules may mediate retinal leukocyte stasis (leukostasis) in diabetes and a reduction in the leukostasis by anti-adhesion antibodies can suppress retinal vascular leakage. In addition, some agents inhibiting leukostasis are reported to improve retinal abnormalities induced by diabetes. Thus, leukostasis in the retinal microcirculation can be a new promising target in the treatment of diabetic retinopathy.     

首钢职工糖尿病视网膜病变流行病学调查

目的对首钢所属年龄在３０岁以上人群２９９３８例糖尿病视网膜病变的发生率及其危险因素进行调查。方法对确诊为糖尿病的９５５例（３．１９％）中的５３４例进行系统眼部检查，部分行眼底荧光血管造影。结果糖尿病患者５３４例中，９０例有糖尿病视网膜病变（１６．９％）。结论糖尿病视网膜病变与糖尿病病程、治疗方法和空腹血糖水平显著相关。多因素逻辑回归分析表明，糖尿病病程和空腹血糖水平是视网膜病变发生的最主要危险因素。     

首钢职工糖尿病现网膜病变流行病学调查

对首钢所属年龄在３０岁以上人群２９９３８例糖尿病视网膜病变的发生率及其危险因素进行调查。方法对确诊为糖尿病的９５５例中的５３４例进行系统眼部检查，部分眼底荧光血管造影。结果糖尿病患者５３４例中，９０例有糖尿病视网膜病变。     

Longitudinal study examining the risk factors for proliferative retinopathy and maculopathy in type-I diabetes: The Royal College of Physicians of Edinburgh Diabetes Register Group

PURPOSE: The aim of this study was to determine whether there were any differences in the risk factors for developing proliferative diabetic retinopathy or maculopathy in patients with type-I diabetes. METHOD: In all, 1632 patients aged 35 years or younger at diagnosis and treated with insulin, attending six hospital diabetes clinics in Scotland and included on the Royal College of Physicians of Edingburgh Diabetes Register were followed up for a median of 4.0 (2.5-5.5 years: interquartile range). All patients were screened at least annually for diabetic retinopathy using direct ophthalmoscopy, and positive findings were confirmed using slit lamp by an ophthalmologist. RESULTS: Duration of diabetes and HbA1c were the important risk factors for developing proliferative retinopathy, while the duration of diabetes, systolic blood pressure, and HbA1c were the important factors of maculopathy. The adjusted relative incidence for proliferative retinopathy with a HbA1c in the highest quartile was 26.7, while for maculopathy it was only 2.29. Carstairs deprivation score was not associated with either retinal pathology. There was a plateau effect for systolic blood pressure of 140 mmHg and for duration of diabetes of 16 years for developing either maculopathy or proliferative retinopathy. CONCLUSION: Duration of diabetes is a strong predictor for maculopathy and proliferative disease, but is relatively more important for proliferative disease. Raised systolic blood pressure is relatively more important for predicting maculopathy, while raised HbA1c is relatively more important for developing proliferative retinopathy.