Nrf2通路在糖尿病视网膜病变中的研究进展

糖尿病视网膜病变(DR)作为糖尿病的一种严重并发症,可能导致严重的视力下降或丧失.核因子E2相关因子2(Nrf2)是一种在氧化应激及炎症相关组织损伤中发挥重要作用的氧化还原敏感转录因子.越来越多的研究表明,Nrf2在DR的发生和发展中起着重要作用.本文就Nrf2通路在糖尿病、DR发病中的作用及其与血管内皮生长因子(VEGF)表达的相关性进行综述.     

lL-6与糖尿病性视网膜病变的相关研究进展

近年来,随着糖尿病患者的不断增多,糖尿病的并发症之一糖尿病性视网膜病变( diabetic retinopathy,DR)也逐渐成为我国目前及未来防盲、治盲的重点。现在, DR免疫炎症发病机制学说得到了越来越多学者的认同。我们就炎症因子IL-6(interleukin-6,IL-6)在DR中的作用加以综述。     

IL-6与糖尿病性视网膜病变的相关研究进展

近年来,随着糖尿病患者的不断增多,糖尿病的并发症之一糖尿病性视网膜病变(diabetic retinopathy,DR)也逐渐成为我国目前及未来防盲、治盲的重点。现在,DR免疫炎症发病机制学说得到了越来越多学者的认同。我们就炎症因子IL-6(interleukin-6,IL-6)在DR中的作用加以综述。     

糖尿病视网膜病变的炎症机制

糖尿病视网膜病变(diabetic retinopathy,DR)是50岁以上人群主要致盲眼病之一.研究表明,DR的发生与非酶糖基化作用、蛋白激酶C激活、免疫/炎症、多元醇旁路、生长因子、氧化应激、RAS系统及血流动力学改变等假说有关,但其确切机制尚未完全阐明.近年来,炎症机制在DR发生发展中的作用一直受到国内外学者的关注,而肿瘤坏死因子α (TNFα)、黏附分子及血管内皮生长因子(VEGF)、色素上皮衍生因子(PEDF)在糖尿病视网膜病变发病机制中的作用更是研究的热点.本文就炎症因子及炎症相关因子在DR发病机制中作用的研究现状进行综述.     

炎症、抗炎药物与早期糖尿病视网膜病变的关系

糖尿病视网膜病变(DR)是糖尿病严重的微血管并发症，已成为致盲的主要因素之一。目前DR发生机制尚未明确，高血糖诱发一系列相关的功能和生化代谢异常，如血流改变、血液流变学异常、多元醇通路活化、氧化应激增多、晚期糖基化终产物积聚及细胞因子活化等受到广泛关注。近年的研究发现许多炎症因素如白细胞浸润、黏附分子及许多炎症因子的表达与早期DR的发生、发展密切相关；许多抗炎药物可通过抑制白细胞积聚、降低炎症因子表达等过程，阻止或减缓DR的发生与发展。 （中华眼底病杂志，2008，24：312-315）     

NLRP3炎症小体在糖尿病视网膜病变神经血管单元损伤中的机制研究

糖尿病视网膜病变(DR)是神经血管单元(NVU)损伤导致的神经血管性疾病,免疫失衡和炎症反应是影响NVU正常功能,并导致DR进展的关键因素。核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体是一种参与疾病炎症反应的蛋白复合体,其可识别内源性危险信号,激活caspase-1,诱发一系列炎症因子的活化和细胞焦亡。炎症小体的适度激活可以维持和激发固有免疫,抵御细菌和病毒感染;炎症小体过度激活则导致炎症因子的过量表达和持续作用,引发免疫紊乱和炎症级联反应,从而对机体产生严重损伤。本文就近年来NLRP3炎症小体在DR神经血管损伤中的机制及相关药物的调控研究进行综述。     

IL-8与糖尿病视网膜病变

糖尿病视网膜病变(diabetic retinopathy,DR)是最常见的糖尿病微血管并发症之一,然而其具体机制尚不清楚。现在炎症反应作为DR发病机制之一而被越来越多的学者关注,并提出DR是一种炎症性疾病。我们就炎症因子IL-8的特征及其在DR发生发展过程中的作用加以综述。     

补体蛋白调控靶点在糖尿病视网膜病变中的作用及临床研究进展

补体系统是一个具有精密调控机制的蛋白质反应系统，具有介导炎症、调节免疫应答、溶解细胞和清除免疫复合物等功能。糖尿病视网膜病变(DR)是糖尿病常见和严重的眼部并发症，是眼科常见的不可逆性致盲性眼病之一，且其发病机制错综复杂，包括缺氧、氧化应激、炎症反应、多元醇代谢通路的异常等。近年来有越来越多的证据表明，免疫系统的失调和炎症是DR发病的重要因素，且多种补体蛋白在炎症调节、血管新生等关键过程中发挥着重要作用。因此，本综述的中心主旨在于研究补体系统及相关调节蛋白在DR中的作用，目的是阐明多种补体蛋白与DR发生发展的紧密联系，为我们防治DR提供重要参考和新的思路。同时本文也对补体系统靶向药物的临床研究进一步阐述。     

细胞因子信号抑制因子3与糖尿病视网膜病变

糖尿痛视网膜病变(diabetic retinopathy,DR)是一种常见的糖尿病慢性并发症,早期的视网膜血管渗漏和晚期的新生血管形成是其重要的病理改变,而血管内皮生长因子以及各种炎症因子、瘦素、血管紧张素Ⅱ等在英发病中发挥重要作用.细胞因子信号抑制因子3作为调节细胞因子信号通路的一种重要蛋白,通过调节Janus激酶/信号转导转录激活因子(JAK/STAT)信号通路,抑制上述各种因子的作用,成为未来治疗DR的新靶点.本文就细胞因子信号抑制因子3在DR发病中的作用进行综述.     

VEGF在糖尿病视网膜病变发病机制中的作用及抗VEGF靶向治疗新进展

糖尿病视网膜病变(diabetic retinopathy,DR)是糖尿病最常见的并发症之一。DR的发病机制十分复杂,至今尚未完全阐明。目前认为DR患者会出现视网膜毛细血管阻塞,可导致局部缺氧,由此引起促新生血管因子产生增多,其中包括VEGF。VEGF是促新生血管形成的主要因子之一,会降低血管内皮细胞间的紧密连接蛋白表达,参与血管炎症反应、增加血管通透性和促进新生血管形成。近年来有关DR的发病机制以及治疗的研究越来越深入。本文旨在阐述VEGF在DR发病机制中的作用,以及抗VEGF治疗策略的最新进展。     

长链非编码RNA在糖尿病视网膜病变发展及治疗中的研究进展

DR是世界各地工作年龄段成年人失明的主要原因，其发病机制是多因素的，分子机制尚不完全清楚。长链非编码RNA（lncRNAs）被认为是多细胞功能的关键调节因子，已有证据表明其参与了DR的许多病理生理机制，本文就 lncRNAs在DR中发挥功能的分子机制及调控作用进行综述，为今后DR的防治研究提供一定的策略和方向。     

Flow cytometry tear analysis in patients with chronic allergic conjunctivitis

Tears from patients with chronic allergic conjunctivitis were analyzed with flow cytometry to determine the function of the T lymphocyte-related immunological reactions in the disease pathogenesis. Twenty-eight patients and 22 normal volunteers were studied; tears were obtained with capillary tubes. T helper/T suppressor ratios and the percentages of HLA DR+, CD23+, and CD3+ cells were significantly higher in patients than in controls. This study provides support for the hypothesis that chronic allergic conjunctivitis results from T lymphocyte-related immunological reactions.     

Lupus anticoagulant positivity in insulin dependent diabetic patients: an additional risk factor in the pathogenesis of diabetic retinopathy?

AIMS: To investigate whether lupus anticoagulant (LA) positivity, a marker of endothelial dysfunction, might be relevant to the pathogenesis of diabetic retinopathy (DR). METHODS: 32 IDDM patients were examined for LA, fibrinogen, prothrombin (PT), PTT, prothrombin degradation products (F1+2), and activated protein C (APC). RESULTS: APC decreased and F1+2 increased significantly in LA positive but not in LA negative patients; 60% of LA positive and 18% of LA negative subjects had DR. PT, PTT, and fibrinogen levels were insignificant. CONCLUSION: These preliminary findings suggest that LA positivity could represent an additional risk factor for DR, acting as a link between the immunological and haemostatic systems.     

Antibodies to types II and IV collagens, tumor necrosis factor-alpha and circulating immune complexes in lacrimal fluid and serum of patients with diabetic retinopathy and different stages

Clinical and immunological examinations are carried out in patients with preclinical, nonproliferative, preproliferative, and proliferative diabetic retinopathy (DR). On the whole, DR is characterized by a notable increase in antibody-dependent immune response, associated with appearance of antibodies to collagen of the II and IV types in the lacrimal fluid and serum, with the "local" reactions predominating. The level of reactions of cellular autoimmune response (tumor necrosis factor-alpha) and cell-to-cell reactions in the lacrimal fluid and serum is low. Increased level of circulating immune complexes in the serum and almost complete absence of free antibodies to collagen in the blood may be indicative of formation of pathogenic immune complexes precipitating on vascular walls and in other tissues. Various forms of immune response were revealed, conducive to a favorable or unfavorable course of DR.     

糖尿病视网膜病变相关基因多态性的研究进展

糖尿病视网膜病变（DR）是糖尿病最常见、最严重的并发症之一,发病率和致盲率逐年上升。通常认为其发生、发展与血糖控制情况、糖尿病病程长短等因素有关,而发病机制尚未完全明了。现在越来越多的证据表明其与遗传易感性不同有关。DR是一种多基因作用的疾病,近年来的研究已筛选出数十种可能与之相关的基因多态性,其中包括广受关注的血管内皮生长因子基因多态性、一氧化氮合酶基因多态性等。研究它们在DR发生发展过程中的作用机制,对今后DR风险预测、早期诊断及指导治疗具有重要意义。本文将对DR相关基因多态性的研究进展进行综述。     

MicroRNAs在糖尿病视网膜病变中的相关研究进展

MicroRNAs(miRNAs)是一种小分子非编码RNA,是转录后调节基因表达关键因子,参与调控细胞分化、增殖和新陈代谢等多种生物学过程。在糖尿病视网膜病变(DR)发生发展过程中miRNAs表达差异改变明显,国内外多项研究表明miRNAs调控基因的表达与DR生理病理机制关系密切。部分特异性表达的miRNAs可以通过调控视网膜中氧化应激与炎症反应水平等影响DR发生发展,因此通过增强或抑制这部分miRNAs可以延缓DR病情进展。单个或多个miRNAs的组合可以作为DR新型的转录组学生物标志物,也是未来治疗DR的潜在有效靶点。目前针对血液或体液中特定miRNAs的检测有助于DR的早期干预治疗和病情随访追踪。因此,本文主要对miRNAs及其参与调控DR的分子机制、治疗前景及生物标志物的相关研究进展作一综述。     

间充质干细胞治疗早期糖尿病视网膜病变研究进展

糖尿病视网膜病变(DR)是糖尿病的主要并发症之一,其病变主要包括微血管病变和神经元功能的损害.治疗早期DR的研究从未间断,包括药物、生物制剂等,其中间充质干细胞(MSCs)作为一种具有广阔应用前景的组织工程细胞得到越来越多的关注.MSCs具有多向分化及免疫调节等能力,MSCs治疗DR可能有多种机制,通过MSCs体外培养和动物体内实验的研究发现,不同途径移植MSCs对DR进行早期干预后,其对DR的抗炎及神经保护等作用可改善DR视网膜功能,延缓DR的发展.就研究进展作一综述.     

Genetic polymorphism of HLA DR in a Scottish population of patients with pars planitis

PURPOSE: Human leucocyte antigen (HLA) class II influences the immunological susceptibility for a variety of diseases including many types of non-infectious intraocular inflammation. Previous studies on North American patients with pars planitis, a subtype of intermediate uveitis, reported an increased prevalence of HLA DR15 in this population. In contrast, two European studies could not find an association between HLA DR2 or its allelic subtype DR15 and various forms of intermediate uveitis. We therefore investigated the genotype frequency of HLA DR alleles in a Scottish population of patients with typical pars planitis. METHODS: Twenty patients with pars planitis were identified from the uveitis database of Grampian University Hospitals. Only patients with bilateral vitritis and snowbanks in at least one eye in the absence of systemic disease were included in the study. Fifteen patients and 34 healthy controls underwent HLA DR genotyping for all DRB genes using PCR sequence specific primers. RESULTS: HLA DR15 was found in 13% of patients with pars planitis and in 24% of controls. There was no statistically significant difference between these two groups. Furthermore, the frequencies of HLA DR 1, 3-14, and 16 did not differ significantly between patients and controls. CONCLUSIONS: There appears to be no association between the occurrence of pars planitis and the HLA DR15 or other known HLA DR genotypes in Scottish patients. However, the small sample size limits the power of this study.     

神经元退行性病变在糖尿病视网膜病变中的研究进展

糖尿病视网膜病变是糖尿病常见的并发症,作为微血管病变被广泛报道。研究发现视网膜神经元退行性病变在糖尿病视网膜病变早期已经发生,且在糖尿病视网膜病变进展过程中扮演重要角色。神经元退行性病变以神经元凋亡和胶质反应为主要特征,其发生机制包括高血糖、氧化应激、谷氨酸毒性、炎症等。糖尿病视网膜神经退行性病变与微血管病变的发生发展密切相关。     

The pathogenesis of early retinal changes of diabetic retinopathy

Recent successful trials of antibodies to vascular endothelial growth factor (VEGF) in diabetic retinopathy implicate this cytokine as a major cause of diabetic retinopathy (DR) and diabetic macular oedema (DME). The mechanisms which cause VEGF to be over-expressed to cause the vasculopathy are not entirely clear. This review explores the earliest changes to the retina in DR and the factors that predispose or prevent DR, including sleep apnoea, receptor degenerations laser treatment and VEGF polymorphism. The review also presents the evidence that retinal hypoxia, existing in the earliest stages, causes DR. This hypoxia is much increased by dark adaptation, indicating a new and possibly superior therapy.