骨桥蛋白与眼部新生血管性疾病研究进展

眼部新生血管是眼部疾病中致盲的主要原因之一.常见的致盲眼病,如糖尿病视网膜病变、年龄相关性黄斑变性、感染性角膜炎等均与新生血管存在一定的关系.骨桥蛋白（OPN）是一种能够促进血管再生与组织修复的糖蛋白,在角膜、脉络膜和视网膜新生血管中表达增多,能够促进新生血管的发生.OPN与新生血管的关系为新生血管性疾病的研究和治疗提供了新的方向.从OPN促进角膜新生血管、脉络膜新生血管、视网膜新生血管生成3个方面对OPN与眼部新生血管性疾病的关系研究进展进行综述.     

可溶性血管内皮生长因子受体-2及其对眼新生血管抑制作用的研究进展

新生血管形成是很多重要眼部疾病的共同病理改变,血管内皮生长因子（vascularendo-thelialgrowthfactor,VEGF）是血管生成重要的促进因子。近年来,可溶性血管内皮生长因子受体-2（solubleVEGFreceptor-2,sVEGFR-2）被证实为一种VEGF促血管生成信号转导通路的天然抑制剂。有研究表明,它与眼部新生血管的发生发展密切相关,可作为新生血管性眼病的抑制因子及其血清标志物而具有临床应用价值。本文就sVEGFR-2在抗眼部新生血管中作用的研究进展予以综述。     

Retinal and choroidal angiogenesis: pathophysiology and strategies for inhibition

Retinal angiogenesis and choroidal angiogenesis are major causes of vision loss, and the pathogenesis of this angiogenesis process is still uncertain. However, several key steps of the angiogenic cascade have been elucidated. In retinal angiogenesis, hypoxia is the initial stimulus that causes up regulation of growth factors, integrins and proteinases, which result in endothelial cell proliferation and migration that are critical steps in this process. Once the endothelial tube is formed from the existing blood vessels, maturation starts with recruitment of mural cell precursors and formation of the basement membrane. Normally, there is a tight balance between angiogenic factors and endogenous angiogenesis inhibitors that help to keep the angiogenic process under control. Although the steps of choroidal angiogenesis seem to be similar to those of retinal angiogenesis, there are some major differences between these two processes. Several anti-angiogenic approaches are being developed in animal models to prevent ocular angiogenesis by blocking the key steps of the angiogenic cascade. Based on these pre-clinical studies, several anti-angiogenic clinical trials are ongoing in patients with diabetic retinopathy and age-related macular degeneration. This review discusses the pathogenesis of retinal and choroidal angiogenesis, and alternative pharmacological approaches to inhibit angiogenesis in ocular diseases.     

胎盘生长因子在新生血管性眼病中的研究进展

新生血管是许多致盲性眼病的主要原因,例如糖尿病视网膜病变、早产儿视网膜病变、年龄相关性黄斑变性等。血管内皮生长因子( vascular endothelial growth factor, VEGF)在新生血管的形成中起着重要的作用,被认为是作用最强的血管生长因子。胎盘生长因子( placental growth factor, PlGF)是VEGF家族中的一员,可促进新生血管生成,刺激内皮细胞迁移增殖,介导免疫炎症反应,且特异性表达于病理性新生血管,但在正常血管中不表达。因此近年来PlGF逐渐受到人们关注。本文对PlGF在新生血管性眼病中的作用机制进行探讨。     

关注抗血管内皮生长因子药物治疗眼部新生血管疾病的潜在风险

抗血管内皮生长因子（VEGF）药物为眼部新生血管疾病的治疗开辟了新的途径，其有效性和安全性也已经为大量研究工作所证实。但在临床实践中，长期、大剂量的应用抗VEGF药物同时也会带来一些新的问题和并发症，甚至会影响正常眼组织血管生成过程和视网膜的血液供应。因此，必须重视过度抗VEGF治疗眼部新生血管疾病带来的问题和潜在风险。     

色素上皮细胞衍生因子基因治疗视网膜及脉络膜新生血管性疾病研究进展

色素上皮细胞衍生因子（pigment epithelium—derived factor，PEDF）是一种相对分子质量为50000的分泌蛋白，属于丝氨酸超家族的一员。近年来研究发现PEDF具有多种生物学功效，包括抗新生血管，神经营养及神经保护功能。PEDF是最有效的内源性眼部新生血管抑制物。PEDF对于治疗血管增生性疾病及视网膜变性性疾病具有广阔的前景，基因转移为眼内组织治疗药物的持续传递提供了有效途径。就近年来关于PEDF基因治疗视网膜及脉络膜疾病的研究进展给以综述。     

Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases

The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age‐related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis‐dependent pathologies in the eye and non‐ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen‐induced retinopathy, laser‐induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF‐specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research.     

色素上皮细胞衍生因子与脉络膜新生血管性疾病

色素上皮细胞衍生因子(pigment epithelium-derived factor,PEDF)是一种分泌蛋白,相对分子量为50000,属于丝氨酸超家族的一员。近年来大量研究发现PEDF具有多种生物学功效,包括抗新生血管、神经营养及神经保护功能。PEDF是最有效的内源性眼部新生血管抑制物。PEDF对于治疗血管增生性疾病及视网膜变性疾病具有广阔的前景,就近年来关于PEDF的研究进展及其与脉络膜新生血管性疾病的相关研究进展给以综述。     

抗VEGF药物治疗新生血管性眼病的研究进展

新生血管形成是很多重要眼部疾病的共同病理改变,血管内皮生长因子（VEGF）是新生血管形成过程中重要的启动因子。近年来,玻璃体腔注射抗VEGF药物为新生血管性眼病的治疗开辟了新的方向及途径,并取得了很好的效果。本文就近年来出现的几种抗VEGF药物的基础研究、临床应用及不良反应情况予以综述。     

血管内皮生长因子及其受体通道与角膜新生血管的关系研究进展

角膜新生血管(CNV)性疾病是目前致盲的主要原因之一,抑制CNV形成是挽救角膜盲患者视力,提高患者生活质量的重要途径之一.血管内皮生长因子(VEGF)及其受体通道是国内外新生血管性疾病的研究热点,是CNV形成的调节通道之一,是目前公认的较强的血管生长因子.对VEGF及其受体通道、其促血管生成机制、通过抑制VEGF及其受体通道来抑制CNV的研究现状及前景做一综述.     

CD105与脉络膜新生血管

CD105(endoglin)为一种同型二聚体的膜结合性糖蛋白,是转化生长因子-β(transforming growth factor,TGF-β)受体超家族的成员之一。它参与TGF-β受体的信号转导,调节细胞对TGF-β的反应,在新生血管组织及肿瘤组织边缘部分血管起源的内皮细胞中高度表达,是新生血管的标志物之一。脉络膜新生血管(choroidal neovasculariza-tion,CNV)的生成是年龄相关性黄斑变性(age-related macular degeneration,AMD)、眼拟组织胞浆菌病综合征(presumed ocular histoplasmosis syndrome,POHS)和病理性近视黄斑变性等CNV相关疾病的的主要病理特征。近年研究表明,CD105与CNV密切相关,可能成为治疗CNV重要的靶分子之一。     

中药单体对眼部新生血管性疾病治疗作用的研究现状

概述中药单体在眼部新生血管性疾病中的应用现状。通过检索近十余年来国内外相关研究文献,进行归纳和总结,概述中药单体抑制眼内新生血管的研究进展,阐述中医药在眼内新生血管研究领域具有的潜在优势,为眼部新生血管性疾病的研究及治疗提供新的思路和参考。     

Avastin在眼科应用的研究进展

Avastin是第一个被美国FDA批准的通过抑制血管生成发挥抗癌作用的新药,是现行几种抗血管生成制剂之一,可抑制血管内皮生长因子(VEGF)的生成,近年研究表明,该药在治疗眼部新生血管性以及渗出性病变中疗效显著,而且价格便宜,应用前景十分广阔。     

康柏西普在眼部新生血管性疾病中的应用进展

康柏西普是中国自主研发的一种抗血管内皮生长因子新药。自从2013年被中国国家食品药品管理总局批准用于临床,康柏西普在治疗湿性年龄相关性黄斑变性、脉络膜新生血管、黄斑水肿等眼部新生血管性疾病过程中显示出可靠的安全性和疗效。针对不同的疾病,康柏西普的治疗策略有所不同。本文就近年来康柏西普在湿性年龄相关性黄斑变性、糖尿病性黄斑水肿、病理性近视脉络新生血管、新生血管性青光眼、未成熟儿视网膜病变、角膜新生血管等眼部新生血管性疾病中的应用进展进行综述,总结探讨康柏西普的用药适应证、给药方案和治疗效果。期待康柏西普的用药适应证会更广,给药方案会更多,为眼部新生血管性疾病的治疗带来新的思路。     

血管内皮生长因子及其受体在眼科的应用研究进展

眼部新生血管的形成是一个及其复杂的病理生理过程,受多种因子的调节,目前血管内皮生长因子（vascular endothelial growth factor,VEGF）被认为是新生血管形成过程中关键性因子之一.已发现的血管内皮生长因子包括：VEGF-A、VEGF-B、VEGF-C、VEGF-D、VEGF-E、VEGF-F以及胎盘生长因子（placenta growth factor,PIGF）;VEGF受体（VEGF receptor,VEGFR）包括：VEGFR-1、VEG-FR-2、VEGFR-3.各受体可被不同或相同的VEGF激活、调控着不同的生理功能,其中对VEGF-A及其受体的研究最为深入.基于VEGF-A及其受体对新生血管不同作用位点和方式的研究,各种药物应运而生,使临床针对眼部新生血管性疾病的用药和治疗方案也发生了革命性的改变.但随着对VEGF家族及其受体的深入研究,逐渐发现VEGF家族中的其他成员,如：VEGF-B等与VEGF-A的作用靶器官及作用机制有很大差别.本文就VEGF家族中各成员及其受体的作用机制和功能以及目前抗VEGF的相关药物的种类、临床应用和研究进展进行综述.     

Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration

Angiogenesis has a causal role in many diseases, including neovascular age-related macular degeneration (AMD). Identification of key regulators of angiogenesis, including vascular endothelial growth factor (VEGF), fibroblast growth factor 2, pigment epithelium-derived growth factor, angiopoietins and extracellular matrix molecules, has facilitated the development of novel therapeutic agents that target the underlying pathological angiogenic process. Among these, VEGF serves as a "master switch" for many ocular neovascular conditions through its promotion of endothelial cell proliferation and survival, vascular permeability and ocular inflammation. Two anti-VEGF agents are now clinically available: bevacizumab, an antibody for metastatic colorectal cancer, and pegaptanib sodium, an aptamer for neovascular AMD. Unlike bevacizumab, which binds all VEGF isoforms, pegaptanib targets only VEGF165, the isoform responsible for pathological ocular neovascularization and thus an ideal target for treatment of AMD. Although other therapies targeting angiogenesis in AMD are in clinical development, to date, pegaptanib is the only therapy approved by the Food and Drug Administration of the United States for the treatment of all neovascular AMD and represents a valuable addition to the hitherto limited options available for patients.     

血管内皮生长因子的神经保护作用

血管内皮生长因子,也称血管通透性因子,可以促进血管内皮细胞的增生和迁移,以及增加血管的通透性。此外,VEGF家族还与淋巴管生成、炎症反应、造血作用以及神经保护作用等有关。在缺血、缺氧或氧化应激等情况下,VEGF可以通过增加组织灌注、抑制细胞凋亡、刺激神经再生等方式起到神经保护作用。因此,VEGF在神经退行性疾病、脑卒中等神经系统疾病中的治疗作用逐渐引起重视。另一方面,抗VEGF疗法在眼部病理性新生血管性疾病的治疗中可能会导致相应的不良反应。就VEGF神经保护作用的机制及其在神经系统疾病和眼部疾病中的作用进行综述。     

IGF-1与脉络膜新生血管性疾病

在脉络膜新生血管(choroidal neovascularization,CNV)的发生发展过程中,许多生长因子发挥了一定的作用.近来发现胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)不仅参与胚胎发育、创伤修复和肿瘤生长等过程的调节,而且还是一种眼内促生长的促血管生成因子,参与了CNV的形成.现对IGF-1与CNV形成关系的研究进展作一综述.     

Bevacizumab in glaucoma: a review

Recent research has shown that a large number of growth factors are responsible for neovascularization. Vascular endothelial growth factor has been identified as playing a key role in ocular angiogenesis. Bevacizumab, a humanized monoclonal antibody that binds to all isoforms of vascular endothelial growth factor, has shown promising results in regression of neovascularization. The use of bevacizumab has been reported extensively in various retinal pathologies, including proliferative diabetic retinopathy, cystoid macular edema, neovascular age-related macular degeneration, and neovascular glaucoma, but the clinical use in glaucoma is not yet clear. Glaucoma filtering surgery entails fashioning an external filter for aqueous drainage, and a prerequisite to its optimum functioning is a patent filtering bleb. Since fibroblast function and growth of new vessels is a component of healing of the bleb, there have been attempts to retard this healing by the use of bevacizumab. This article reviews current clinical studies documenting the use of bevacizumab in glaucoma.     

正确理解新生血管性疾病的发病机制，合理行使抗新生血管药物治疗

血管内皮生长因子（VEGF）是眼内新生血管形成过程中起关键作用的中心环节，抗 VEGF治疗是眼内新生血管性疾病治疗的突破点。抗新生血管药物玻璃体腔注入是一种安全、 有效的治疗眼部新生血管性及渗出性疾病的方式，具有生物相容性好，价格低，玻璃体内半 衰期较长，不需要频繁注射等优点；但目前缺乏多中心研究，其长期效果和安全性有待进一步临床验证。新生血管的病因、类型不同，治疗反应也不一样；同样的新生血管，治疗方式也不尽相同，需要正确理解新生血管性疾病的发病机制，合理选择治疗方式，努力探索安全、有效、经济、方便的 治疗新方法。 （中华眼底病杂志，2008，24：157-159）