血管内皮生长因子与视网膜新生血管性疾病

血管内皮生长因子（ＶＥＧＦ）是新近确定的一种特异性刺激血管内皮细胞增殖及新生血管形成的生长因子。视网膜血管内皮细胞存在ＶＥＧＦ高亲和受体，而且受体数目较其它组织内皮细胞多。ＶＥＧＦ的特点是它的表达受局限部氧浓度的调节。视网膜血管内皮细胞、色素上皮细胞、周皮细胞、Ｍｕｅｌｌｅｒ细胞均能合成并分泌ＶＥＧＦ，缺氧可上调其基因表达。ＶＥＧＦ既可刺激视网膜血管内皮细胞增殖及移行，也可诱导视网膜新生血管形成。     

血管内皮生长因子与视网膜新生血管性疾病

血管内皮生长因子（ＶＥＧＦ）是新近确定的一种特异性刺激血管内皮细胞增殖及新生血管形成的生长因子。视网膜血管内皮细胞存在ＶＥＧＦ高亲和受体，而且受体数目较其它组织内皮细胞多。ＶＥＧＦ的特点是它的表达受局部氧浓度的调节。视网膜血管内皮细胞、色素上皮细胞、周皮细胞、Ｍüｌｅｒ细胞均能合成并分泌ＶＥＧＦ，缺氧可上调其基因表达。ＶＥＧＦ既可刺激视网膜血管内皮细胞增殖及移行，也可诱导视网膜新生血管形成。视网膜新生血管性疾病患者玻璃体ＶＥＧＦ含量增高。组织学定位表明ＶＥＧＦ的表达主要在内核层、神经节细胞层、ＲＰＥ细胞及Ｍüｌｅｒ细胞。阻断ＶＥＧＦ的产生及生物活性，有助于治疗视网膜新生血管性疾病     

血管内皮生长因子与视网膜缺血性病变

视网膜中央静脉阻塞和增殖性糖尿病视网膜缺血性病变等常伴有眼内新生血管的形成。近年的研究表明，血管内皮生长因子（ＶＥＧＦ）是一种特异性内皮细胞有丝分裂原，可刺激内皮细胞增殖。视网膜缺氧产生的ＶＥＧＦｍＲＮＡ表达升高，在新生血管的形成过程中发挥重要作用。本文主要对ＶＥＧＦ的作用，以及ＶＥＧＦ与眼内新生血管形成之间的关系加以综述     

血管内皮生长因子与视网膜缺血性病变

视网膜中央静脉阻塞和增殖性糖尿病视网膜缺血性病变等常伴有眼内新生血管的形成。近年的研究表明，血管内皮生长因子（ＶＥＧＦ）是一种特异性内皮细胞有丝分裂原，可刺激内皮细胞增殖。视网膜缺氧产生的ＶＥＧＦ ｍＲＮＡ表达升高，在新生血管的形成过程中发挥重要作用。本文主要对ＶＥＧＦ的作用，以及ＶＥＧＦ与眼内新生血管形成之间的关系加以综述。     

血管内皮生长因子在糖尿病新生血管性青光眼虹膜组织中的表达

目的 探讨血管内皮生长因子（ＶＥＧＦ）在糖尿病虹膜新生血管发生中的作用。方法 收集糖尿病新生血管性青光眼虹膜组织２５例,免疫组织化学染色,光镜观察。结果 ＶＥＧＦ在新生血管性青光眼虹膜组织中的阳性率为１００％,而在对照组中的阳性率为２１．０５％,χ＾２＝２９．９５,Ｐ〉０．００５。ＶＥＧＦ主要表达于虹膜表面的新生血管内皮细胞中。结论 糖尿病新生血管性青光眼虹膜组织中ＶＥＧＦ表达异常增高,虹膜表面的新生血管内皮细胞可以通过自分泌ＶＥＧＦ来刺激新生血管快速生长。     

血管内皮生长因子与大鼠角膜移植术后新生血管增生关系的实验研究

目的：观察血管内皮生长因子（ｖａｓｃｕｌａｒ ｅｎｄｏｔｈｅｌｉａｌ ｇｒｏｗｔｈ ｆａｃｔｏｒ,ＶＥＧＦ）在大鼠角膜移植术后不同时间点的表达及与角膜新生血管（ＣＮＶ）生长之间的关系。方法：利用免疫组化方法观察同种异体大鼠角膜移植术后不同时间点ＶＥＧＦ的表达。结果：角膜移植术后,ＶＥＧＦ组ＣＮＶ生长面积与其它各组差异有高度显著性（Ｐ〈０．０１）,生长时间提前,高峰期持续时间长,ＶＥＧＦ表达明显强,     

血管内皮生长因子在视网膜缺血性病变中的应用研究

视网膜缺血性病变是一种严重的眼内病变 ,常伴有眼内新生血管形成 ,可导致严重的眼内并发症 ,如增殖性玻璃体视网膜病变 ,新生血管性青光眼和眼内出血等。近年来 ,许多学者认为视网膜缺血性病变新生血管的发生发展与血管内皮生长因子 (ＶＥＧＦ)有着密切的关系。一、ＶＥＧＦ的     

地塞米松抑制碱烧伤后角膜新生血管的实验研究

目的：探讨地塞米松对角膜新生血管形成及角膜内血管内皮生长因子（ＶＥＧＦ）的影响。方法：采用碱烧伤的方法制备家兔角膜新生血管模型,分为三组,每日结膜下注射地塞米松０．５毫克组、１．０毫克组、对照组。分别采用宏观测量新生血管长度及生长速度,免疫组化染色检查ＶＥＧＦ蛋白的表达,显微镜下微血管计数方法研究角膜新生血管形成及抑制情况。结果：实验组新生血管生长速度变慢,微血管数量减少,ＶＥＧＦ蛋白表达下降,具     

血管内皮生长因子在鼠角膜新生血管模型的表达

正常角膜透明无血管 ,而角膜局部和全身因素均可导致角膜新生血管 (ｃｏｒｎｅａｌｎｅｏｖａｓｃｕｌａｒｉｚａｔｉｏｎ ,ＣＮＶ)增生。角膜致盲的主要原因为角膜新生血管性病变。ＣＮＶ可促进组织的修复 ,但严重影响角膜的透明性 ,致使视力下降 ,增加了角膜移植术后排斥反应的发生率。目前的研究表明 ,血管内皮生长因子 (ｖａｓｃｕｌａｒｅｎｄｏｔｈｅｌｉａｌｇｒｏｗｔｈｆａｃｔｏｒ,ＶＥＧＦ)是作用于血管内皮细胞的多肽类因子 ,可增加毛细血管通透性 ,促进新生血管的形成[1 3 ] 。我们观察大鼠正常角膜及损伤后角膜中ＶＥＧＦ的表…     

VEGF在糖尿病性视网膜病变发病机制中的作用及抗VEGF治疗新进展

糖尿病性视网膜病变是世界新发致盲因素之一。血管内皮生长因子（ｖａｓｃｕｌａｒｅｎｄｏｔｈｅｌｉａｌｇｒｏｗｔｈｆａｃｔｏｒ,ＶＥＧＦ）是糖尿病性视网膜病变发病机制中的关键因子,成为近年研究的热点。近年来,抗ＶＥＧＦ药物成为新生血管性及血管性眼底疾病的重要治疗药物,本文就ＶＥＧＦ在糖尿病性视网膜病变病理进程中的作用及抗ＶＥＧＦ治疗新进展作一综述。     

抗血管内皮生长因子Bevacizumab在眼部新生血管中的应用新进展

眼部新生血管性病变是致盲的主要原因之一,大量的研究证据表明血管内皮生长因子(vascular endothelial growth factor,VEGF)是新生血管形成的关键调控因子。Bevaci-zumab是世界上首个批准上市的血管内皮因子抑制剂由于其强大的抗新生血管作用,在眼科新生血管性疾病治疗中有广泛的应用前景。本文对VEGF的特性、VEGF在眼部新生血管形成中的作用和Bevacizumab作用机制、应用范围进行综述。     

Generation and characterization of a recombinant adenovirus expressing vascular endothelial growth factor for studies of neovascularization in the eye.

There is accumulating evidence that an increased expression of vascular endothelial growth factor from retinal pigment epithelial cells may be important in choroidal neovascularization. In vivo studies have demonstrated that subretinal injection of recombinant adenovirus vectors produces long-term transgene expression specifically within retinal pigment epithelial cells. A recombinant adenovirus encoding of vascular endothelial growth factor (Ad.RSV.VEGF) was therefore produced and characterized in order to determine whether an upregulation of vascular endothelial growth factor expression is sufficient to induce choroidal neovascularization. Ad.RSV.VEGF was produced by homologous recombination and its identity confirmed by restriction enzyme analysis. Ad.RSV.VEGF was characterized in vitro by the transduction of cultured retinal pigment epithelial cells. The in vitro characterization confirmed vascular endothelial growth factor mRNA and protein expression from Ad.RSV.VEGF and demonstrated the biological activity of the vascular endothelial growth factor protein. A preliminary in vivo study suggested that the subretinal injection of Ad.RSV.VEGF induced vascular leakage.     

VEGF在糖尿病视网膜病变破坏血-视网膜屏障机制中的研究新进展

糖尿病视网膜病变(DR)是成年人视力下降甚至失明的常见原因之一,由多种发病机制共同作用,其机制虽尚未完全阐明,但血-视网膜屏障破坏是DR的关键过程。血管内皮生长因子(VEGF)作为高度内皮特异的促血管内皮生长因子,是视网膜病理性新生血管形成、破坏血-视网膜屏障的关键因子,因此全面地了解VEGF促进DR血-视网膜屏障破坏的病因病机,成为深入探索DR发病机制的关键。文章围绕DR探讨了VEGF与视网膜血管内皮细胞间的通透性、血管炎性反应、细胞凋亡反应、氧化应激、线粒体损伤以及内质网应激之间的相关机制,以期为VEGF在DR破坏血-视网膜屏障机制研究提供参考。     

Angiogenesis and retinal diseases

Angiogenesis is the process involving the growth of new blood vessels from preexisting vessels which occurs in both physiologic and pathological settings. It is a complex process controlled by a large number of modulating factors, the pro-and antiangiogenic factors. The underlying cause of vision loss in proliferative retinal diseases, such as age-related macular degeneration and proliferative diabetic retinopathy, are increased vascular permeability and choroidal neovascularization, and vascular endothelial growth factor (VEGF) plays a central role in this process. VEGF is produced in the eye by retinal pigment epithelium (RPE) cells and is upregulated by hypoxia. There are four major biologically active human isoforms, of which VEGF165 is the predominant in the human eye and appears to be the responsible for pathological ocular neovascularization. Besides being a potent and specific mitogen for endothelial cells, VEGF increases vascular permeability, inhibits endothelial cells apoptosis, and is a chemoattractant for endothelial cell precursors. VEGF is not the only growth factor involved in ocular neovascularization. Basic fibroblast growth factor (bFGF), angiopoietins, pigment epithelium-derived factor (PEDF), and adhesion molecules also play a role in the pro- and antiangiogenic balance. Advances in the understanding of the bases of pathological ocular angiogenesis and identification of angiogenesis regulators have enabled the development of novel therapeutic agents. Anti-VEGF antibodies have been developed for intravitreal use, and other approaches are currently under investigation. These new drugs may be powerful tools for the treatment of the leading causes of irreversible blindness in people over age 65.     

PIGF在湿性黄斑变性中的作用探讨

脉络膜新生血管是湿性黄斑变性( neovascularage-related macular degeneration,nAMD)的主要发病机制,而血管内皮生长因子( vascular endothelial growth factor,VEGF)促进新生血管的作用已受到广泛认可,目前针对VEGF不同靶点的药物已广泛运用于治疗 nAMD。胎盘生长因子( placental growth factor,PIGF)是抗VEGF的一个新靶点,与VEGF-A有协同作用,可促进新生血管,刺激内皮细胞迁移增殖,介导免疫炎症反应,且在已成熟血管上无表达,特异性较高。本文就PIGF在nAMD中的作用进行探讨。     

Effects of growth-factor combinations on vascular endothelial cell growth in vitro.

Abnormal elevation of growth factors in ocular fluid and serum has been claimed to be a major positive regulator of diabetic retinopathy. In this study, we aimed to explore the individual and collective actions of insulin, insulinlike growth factor I (IGF-I), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-beta) on the proliferation of vascular endothelial cells. Thus, primary human umbilical vein (HUVECs) endothelial cells (ECs) were used to examine their effects by direct viable cell counting and cell-proliferation assay. Insulin, IGF-I, and VEGF individually increased both cell number and proliferation status in a dose-dependent fashion. TGF-beta significantly potentiated the stimulatory effects of insulin and VEGF on EC proliferation, but revealed no synergism with double and triple growth-factor combinations. Our findings emphasize the complexity of the role of TGF-beta in the regulation of EC proliferation. TGF-beta plays an important role in the EC proliferation and the pathogenesis of diabetic retinopathy.     

生长因子诱导的血管内皮细胞增殖作用的研究

目的 研究生长因子对血管内皮细胞增殖活动的诱导和刺激作用。以进一步探讨生长因子在视网新生血管疾病中所起的作用。方法 采用血管内皮生长因子（VEGF）和碱性成纤维生长因子（bFGF）诱导离体培养的血管内皮细胞的增殖。研究VEGF及bFGF对血管内皮细胞DNA合成、细胞生长和细胞周期的调控，以及两种因子的协同效应。结果 VEGF及bFGF均可显著刺激血管内皮细胞的增生，其刺激效应与生长因子浓度呈剂量依赖关系。共同作用时，具有协同效应。两种因子均可显著增加^3H-TdR的掺入量，其刺激作用与浓度呈剂量依赖关系，共同作用时亦具有协同效应。VEGF和bFGF均可显著地产加S期细胞的比例。结论 VEGF及bFGF均可显著地刺激内皮细胞的增殖，促进细胞DNA的合成。两种因子联合应用时，具协同效应。提示：两种生长因子在视网膜新生血管的发生和发展中可能具有一定作用，且存在因子间的协同效应。     

Expression of growth factors in the conjunctiva from patients with active trachoma

PURPOSE: The blinding complications of trachoma are associated with progressive conjunctival fibrosis due to excessive accumulation of extracellular matrix (ECM) components. We studied the processes involved in the regulation of fibrosis in trachoma by investigating the expression of the fibrogenic and angiogenic connective tissue growth factor (CTGF) and basic fibroblast growth factor (bFGF), the angiogenic vascular endothelial growth factor (VEGF), the angiogenesis-associated endothelial cell marker CD105 (endoglin), and the ECM protein tenascin in the conjunctiva. METHODS: Conjunctival biopsy specimens from six patients with active trachoma, and six control subjects were studied by immunohistochemical techniques using monoclonal and polyclonal antibodies directed against CTGF, bFGF, VEGF, CD105, and tenascin. RESULTS: In the normal conjunctiva, weak immunoreactivity for VEGF was observed in epithelial cells. There was no immunoreactivity for the other antibodies. In all trachoma specimens, immunoreactivity for CTGF and bFGF was localized in monocytes/macrophages, positive for the CD68 marker. Strong immunoreactivity for VEGF was observed in epithelial cells and on vascular endothelial cells. CD105 immunoreactivity was observed on vascular endothelial cells. Immunoreactivity for tenascin was noted in the upper substantia propria. CONCLUSIONS: These findings suggest that macrophages play an active role in conjunctival scarring, upregulated local production of CTGF, bFGF, and VEGF contributes to both fibrous tissue growth and angiogenesis, vascular endothelial cells are activated and are undergoing active angiogenesis, and deposition of tenascin reflect remodelling of the conjunctiva in trachomatous conjunctivitis.     

兔视网膜静脉阻塞眼视网膜新生血管组织中 血管内皮生长因子mRNA的表达

目的探讨血管内皮生长因子(vascular endothelial growth factor,VEGF )在视网膜新生血管组织的发生发展中的参与机制。方法 采用氩激光直接光凝法封闭兔眼视网膜静脉建立视网膜静脉阻塞(retinal vein occlusion,RVO)模型。利用组织原位杂交法观察缺血视网膜组织及新生血管组织中VEGF mRNA的表达。结果缺血视网膜及新生血管组 织中有不同程度的VEGF mRNA表达,表达的程度以视网膜新生血管组织中最强。 VEGFmRNA 的表达部位与视网膜组织缺血的分布具有一定的对应性。结论VEGF在视网膜血管增生性病变的发生中可能具有重要的参与机制。(中华眼底病杂志,2001,17:5-7)