基于视网膜神经血管单元损伤及其耦联失衡防治糖尿病视网膜病变的研究进展

糖尿病视网膜病变(DR)作为常见的糖尿病并发症之一,是导致失明的主要原因。传统上,DR主要被认为是一种微血管疾病,随着研究的进展,目前认为神经-胶质-血管单元(NVU)破坏及其耦联机制(coupling)失衡在DR发病的早期起到了关键作用。了解NVU的细胞和分子基础,以及糖尿病如何改变正常的细胞通讯和破坏细胞环境,对DR的早期防治具有重要的意义。本文总结视网膜NVU及其参与DR发病分子机制,基于视网膜NVU修复的DR治疗,并对DR未来发展前景及问题进行探讨。     

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。     

氧化应激在糖尿病视网膜病变中的作用及机制

糖尿病视网膜病变(Diabetic Retinopathy,DR)是临床上糖尿病患者出现的较为常见的并发症,也是糖尿病患者严重的微血管并发症之一糖尿病视网膜病变的发生原因较多,目前发病机制尚不明确,而氧化应激(OS)与DR的发生发展存在一定的相关性,参与并促进病变的发展.因此,本文对糖尿病视网膜病变氧化应激产生的原因与机制、氧化应激对视网膜组织的损伤机制等进行综述,以期更好的了解氧化应激与糖尿病视网膜病变的关系,为抗氧化疗法应用于糖尿病视网膜病变的治疗提供理论依据.     

糖尿病视网膜病变中视网膜小胶质细胞活化及干预机制研究进展

糖尿病视网膜病变(diabetic retinopathy,DR)是糖尿病(diabetes mellitus,DM)最常见的并发症,其发病率随DM病程的延长而增高.DR是一种高发病率和高致盲率的疾病,对DR的发病机制研究一直是国内外的热点之一.但是DR的发病机制尚未完全阐明,近年来,越来越多的学者认为DR可能是一种慢性、低度炎性反应.小胶质细胞(microglia,MG)是视网膜中的单核巨噬细胞,具有抗原呈递功能,DR中MG被活化,释放大量炎症因子,参与DR的炎症反应.了解DR中MG的活化机制,可更好地为DR的预防和治疗开辟新的视角.因此,本文就DR中视网膜MG活化及干预机制进行综述.     

自噬与HMGB1在糖尿病视网膜微血管病变和神经退行性变中的研究进展

糖尿病视网膜病变（diabetic retinopathy,DR）是由糖尿病所导致的最典型的微血管并发症之一。以往DR发病机制和治疗的研究主要集中在微血管;近年来,许多学者认为DR不仅仅是一种微血管病变,而且还伴有视网膜神经退行性变。近期研究表明,自噬与高迁移率族蛋白B1（high mobility group box protein 1,HMGB1）通过多条通路参与到糖尿病视网膜微血管病变和神经退行性变中,通过调控自噬或 HMGB1可能为DR治疗提供一种新的思路。本文就自噬与 HMGB1 在糖尿病视网膜微血管病变和神经退行性变发病中的研究进展进行综述。     

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。     

糖尿病视网膜病变的药物治疗

糖尿病视网膜病变（diabetic retinopathy,DR)是糖尿病最常见和最严重的并发症之一，对DR发病机制的研究为DR的药物治疗提供了思路。本文就抑制蛋白非酶糖基化终端产物，多元醇通路，DAG－PKC信号道路，抑制细胞因子；抗氧化和拮抗粘附分子几方面介绍了DR的治疗药物及研究思路。     

CXC趋化因子及其受体在糖尿病视网膜病变中的作用

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,是目前世界范围内致盲的主要原因之一.DR发生时患者血清及玻璃体内CXC族趋化因子及其受体表达上调,异常表达的CXC族趋化因子及其受体可引起视网膜的低度炎症、信号通路激活以及新生血管形成,进而导致DR的发生.但各种趋化因子在DR中的作用机制仍需进一步研究,为DR患者提供更多的靶向治疗.     

补体功能失调对糖尿病视网膜病变的影响

糖尿病视网膜病变(DR)是糖尿病常见的神经和微血管并发症之一,也是20~74岁人群发生视力障碍的主要原因之一。DR的发病机制至今仍未完全阐明,近年来补体功能失调在DR中的作用受到关注。补体因子及补体调节蛋白异常影响视网膜血管周细胞、内皮细胞、神经细胞及胶质细胞的命运和功能,因而可能作为DR治疗的新靶点。就眼内补体的特点,DR与补体功能失调关系的研究进展,DR中补体基因的多态性和靶向补体分子的探索性治疗成果进行综述,为开展相关研究提供新的思路。     

巨噬细胞在糖尿病视网膜病变中的作用

糖尿病视网膜病变(diabetic retinopathy,DR)是糖尿病常见且严重的微血管并发症,是视力损害的重要原因之一,其发生和发展是一个多细胞参与,多因素调控的复杂过程.巨噬细胞来源于单核细胞,是视网膜主要的炎性细胞,参与视网膜的许多病理和生理过程.随着越来越多的研究着眼于DR病程中炎症的作用,人们发现巨噬细胞对DR的发病机制研究有着重要意义.     

Rho/ROCK pathway and neural regeneration: a potential therapeutic target for central nervous system and optic nerve damage

Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous system (CNS) disorders, and involved in many aspects of neuronal functions including neurite outgrowth and retraction. In the adult CNS, the damaged neuron regeneration is very difficult due to the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp), etc. The effects of these axon growth inhibitors are reversed by blocking the Rho/ROCK pathway in vitro, and the inhibition of Rho/ROCK pathway can promote axon regeneration and functional recovery in the injured CNS in vivo. In addition, the therapeutic effects of the Rho/ROCK inhibitors have also been demonstrated in some animal models and the Rho/ROCK pathway becomes an attractive target for the development of drugs for treating CNS disorders. In this review, we summarized on the effect of the Rho and the downstream factor ROCK in neural regeneration, and the potential therapeutic effect of Rho/ROCK inhibitors in the survival and axonal regeneration of retinal ganglion cells was also discussed.     

Rho/ROCK信号通路参与年龄相关性黄斑变性调控机制的研究现状

年龄相关性黄斑变性（AMD）已被认为是最严重的眼科疾病之一。遗传、老化、氧化应激和炎症等在AMD发生发展中起着重要作用,而且Rho激酶在很多细胞周期过程中发挥着重要作用,Rho/ROCK通路的异常激活参与了AMD的发病过程。本文对Rho/ROCK信号通路的结构、活化、功能、调控AMD的病理机制以及靶向Rho/ROCK通路治疗AMD的潜力进行综述。     

ROCK inhibitors in ophthalmology: A critical review of the existing clinical evidence

Rho kinase (ROCK) inhibitors have emerged as a key therapeutic class of interest in ophthalmology over the last decade. Promising in vitro studies laid the foundations for the development of novel therapeutic agents that target the ROCK signalling pathway in ocular disease, with subsequent clinical trials supporting their use. Corneal endothelial disease, glaucoma, and vitreoretinal disease are the major pathologies in which ROCK inhibitors have been investigated to date. Ripasudil and netarsudil represent the current leaders in this pharmaceutical group, having been extensively validated and approved for use in glaucoma in some countries. Less substantial evidence exists for fasudil in ophthalmic use. ROCK inhibitors are also increasingly used in cultured endothelial cell grafting and as an adjunct to aid in endothelial cell migration and replication in Descemet's stripping procedures or Descemet's membrane injuries. This review has synthesised both established and emerging research to provide a practical guide to prescribing in this drug class. Drug efficacies, side effect profiles, and the demographic and clinical characteristics of appropriate drug candidates are discussed.     

糖尿病视网膜病变的诊断和治疗:2016-2018年最新研究进展

糖尿病视网膜病变（diabetic retinopathy,DR）是糖尿病的一种威胁视力的并发症,是致盲的主要原因。DR发病机制复杂,目前尚不明确。大量的证据使人们意识到DR不仅是一种血管疾病,而且是一种神经退行性疾病。目前针对DR治疗方案效果有限,DR的早期诊断、防治至关重要。本文就近两年DR的诊断、治疗的最新研究进展及新的治疗靶点进行综述。     

自噬的分子机制及其在糖尿病视网膜病变中的作用

糖尿病视网膜病变（diabetic retinopathy,DR）是糖尿病微血管并发症之一,具有特征性的眼底表现,是临床上导致糖尿病患者失明的重要原因。近年来DR的发病率显著增长,严重威胁到糖尿病患者的身心健康,已成为关乎民众健康乃至国计民生的社会问题。DR发病机制复杂,多种因素如氧化应激、缺氧、炎症反应、内质网应激、多元醇途径等,均被证实与DR的发病密切相关。近年研究发现,自噬作为机体一种重要的防御机制,参与了DR的发生与发展,其病理过程涉及多种信号转导通路,与氧化应激、缺氧及新生血管形成尤为相关。因此,自噬与DR的关系成为临床研究的热点。     

Thrombin-induced phosphorylation of the regulatory light chain of myosin II in cultured bovine corneal endothelial cells

PURPOSE: Phosphorylation of the regulatory light chain of myosin II (referred to as myosin light chain or MLC) leads to a loss of barrier integrity in cellular monolayers by an increase in the contractility of the cortical actin cytoskeleton. This effect has been examined in corneal endothelial (CE) cells. METHODS: Experiments were performed using cultured bovine CE cells (BCEC). MLC phosphorylation was induced by a thrombin-mediated activation of the proteinase-activated receptor-1 (PAR-1). Expression of MLC kinase (MLCK), a Ca2+/calmodulin-dependent protein kinase that phosphorylates MLC at its Ser-19 and Thr-18 residues, was determined by RT-PCR and Western blotting. Expression of PAR-1, RhoA, and Rho kinase-1 (effector of RhoA) was ascertained by RT-PCR. MLC phosphorylation was assessed by urea-glycerol gel electrophoresis followed by immunoblotting. The effects of Rho kinase-1 and PKC were characterized by using their selective inhibitors, Y-27632 and chelerythrine, respectively. Reorganization of the cytoskeleton was evaluated by the phalloidin staining of actin. [Ca2+]i was measured using Fura-2. The barrier integrity was assayed as permeability of BCEC monolayers to horseradish peroxidase (HRP; 44 kDa). RESULTS: RT-PCR showed expression of MLCK, PAR-1, Rho kinase-1, and RhoA. Western blotting indicated expression of the non-muscle and smooth muscle isoforms of MLCK. Exposure to thrombin induced an increase in [Ca2+]i with the peak unaffected by an absence of extracellular Ca2+. Pre-exposure to thrombin (2 U ml(-1); 2 min) led to mono- and di-phosphorylation of MLC. Under both basal conditions and in the presence of thrombin, MLC phosphorylation was prevented by chelerythrine (10 microm) and Y-27632 (<25 microm). Thrombin led to inter-endothelial gaps secondary to the disruption of the cortical actin cytoskeleton, which under resting conditions was organized as a perijunctional actomyosin ring (PAMR). These responses were blocked by pre-treatment with Y-27632. Thrombin also increased permeability to HRP, which was abolished by pre-treatment with Y-27632. CONCLUSIONS: Thrombin induces MLC phosphorylation in BCEC. The consequent increase in the contractility of the actin cytoskeleton produces a centripetal force resulting in inter-endothelial gaps and a breakdown of barrier integrity. These responses are PKC- and Rho kinase-dependent. [Ca2+]i increase, as well as sensitivity of the thrombin response to PKC and Rho kinase inhibitors, are consistent with the expression of PAR-1 receptors in BCEC. Thrombin-induced hyperpermeability is a model to investigate barrier dysfunction induced by MLC phosphorylation.     

白内障术后角膜病变治疗的新进展

白内障患者晶状体超声乳化术后的角膜水肿、干眼、角膜内皮功能失代偿致大泡性角膜病变等严重影响着患者满意度和视觉质量。长期以来,穿透性角膜移植是角膜内皮功能失代偿患者视力恢复的有效方法,但角膜供体缺乏及移植后角膜内皮细胞密度降低等问题仍然无法解决。近年来,角膜内皮移植、局部角膜后弹力层撕除、人工培养角膜内皮细胞植片的移植、Rho激酶抑制剂调节角膜内皮细胞增殖等方面的进展和新手段,为白内障术后角膜内皮功能失代偿患者的治疗带来新思路。     

糖尿病视网膜病变药物治疗的研究进展

糖尿病视网膜病变(diabetic retinopathy,DR)是糖尿病患者常见和严重的并发症之一,是糖尿病患者视力损害的最主要原因。随着对糖尿病发病机制的深入研究,近年来多种药物用于DR的防治并取得了一定疗效,包括糖皮质激素、血管生长因子抑制剂、蛋白激酶C(protein kinase C,PKC)抑制剂、肾素-血管紧张素受体拮抗剂坎地沙坦及非诺贝特等,我们就近年来药物治疗DR的现状及进展作一综述。     

血管内皮生长因子抑制剂在糖尿病性视网膜病变中的应用

眼部新生血管是糖尿病性视网膜病变致盲的主要病理改变,而血管内皮生长因子（vascular endothelial growth factor,VEGF）在新生血管形成过程中起关键性刺激作用。VEGF抑制剂主要通过与VEGF结合并阻断其生物活性而起作用,从而达到抑制眼部新生血管生成的目的,在糖尿病性视网膜病变血管渗漏及新生血管形成的治疗中取得了显著的成绩。Bevacizumab（Avastin）是VEGF抑制剂之一,属于重组人源化单克隆抗体,因其疗效良好、价格低廉已被广泛应用于临床。现将VEGF抑制剂（尤其是Avastin）治疗糖尿病性视网膜病变的相关应用进展作一综述。