β肾上腺素能受体拮抗剂治疗眼部新生血管疾病的研究进展

眼部新生血管形成是糖尿病视网膜病变、早产儿视网膜病变、视网膜中央静脉阻塞和老年性黄斑变性等多种眼部疾病的病理学改变, 严重影响患者视力。β受体在结膜、角膜上皮细胞、角膜内皮细胞、眼外肌、小梁网、睫状肌、晶状体和视网膜中均有表达。β肾上腺素能受体拮抗剂与β受体结合, 通过抑制血管内皮生长因子(VEGF)、缺氧诱导因子-1、白细胞介素-6等促血管生成细胞因子, 降低巨噬细胞相关炎症反应, 增加抗血管生成因子表达来发挥抗血管生成作用。其在治疗角膜新生血管、脉络膜新生血管、早产儿视网膜病变时, 可显著减少新生血管面积, 延缓疾病进展, 联合应用抗VEGF药物可减少抗VEGF药物的给药频率。在有效的治疗浓度下, β肾上腺素能受体拮抗剂表现出良好的耐受性;且其较抗VEGF药物有更广泛的靶点, 为角膜、脉络膜和视网膜新生血管等眼部新生血管性疾病提供了新的治疗策略。     

血小板反应蛋白-1在眼部的作用

血小板反应蛋白-1(TSP-1)是一种内源性血管抑制因子,结构复杂,具有多种生物学功能.其在眼部多种组织表达,可调节角膜、视网膜和脉络膜生理和病理性的血管发生,维持眼部组织的无血管化损伤修复,参与维持眼部特有的免疫赦免状态,调节眼压的平衡.阐明TSP-1在眼部生理和病理情况下的作用,特别是明确TSP-1在眼部新生血管性疾病中的血管抑制作用,可为治疗新生血管相关性眼病提供新的思路和治疗靶点.     

半乳糖凝集素与眼部新生血管形成

多种眼部组织都可能形成新生血管,如角膜、虹膜、视网膜和脉络膜等.而病理性新生血管的产生是导致视力损害甚至致盲的重要原因之一,如增生型糖尿病视网膜病变和年龄相关性黄斑变性等.半乳糖凝集素(Galectin)作为凝集素超家族中的一个家族,在人和动物的许多组织中广泛分布.近来许多研究都表明半乳糖凝集素家族参与了细胞黏附、细胞凋亡、炎症反应和肿瘤转移等生理和病理过程,其在肿瘤新生血管中的作用也越来越受到重视,而糖基化也是哺乳动物蛋白转录后修饰的重要方式之一.本文就半乳糖凝集素在眼部新生血管中的作用进行综述.     

环氧化酶-2抑制剂抑制眼部新生血管临床应用新进展

眼部新生血管一直是眼科界的难题之一,发病机制尚未完全清楚.目前,炎症与新生血管的关系成为了研究热点,其中环氧化酶_2(cyclooxygenase-2,COX-2)逐渐受到人们的重视.COX-2与新生血管密切相关,它通过诱导血管内皮生长因子等血管生长因子或其他途径采促进新生血管的生长.近年来,COX-2抑制剂对角膜新生血管、视网膜新生血管、脉络膜新生血管等抑制作用的研究取得进展,本文就COX-2的生物学特性及其抑制剂在抑制眼部新生血管方面的应用作一综述.     

长链非编码RNA与眼部增生性疾病

眼部增生性疾病,如增生性玻璃体视网膜病变(PVR)、糖尿病视网膜病变(DR)、脉络膜新生血管、角膜新生血管等常导致眼结构和功能的损伤,晚期治疗效果差.长链非编码RNA(lncRNA)是一类长度大于200个核苷酸的RNA转录本,虽不能直接编码蛋白质但可通过各种途径调节蛋白编码基因的表达,从而广泛参与调控个体的生长发育以及细胞凋亡、增生、分化等生命活动.越来越多的证据表明lncRNA参与多种眼部疾病的发生和发展,并有望成为其诊断和治疗的新靶点.本文就lncRNA的概念、分类、作用机制及其与PVR、DR、脉络膜新生血管、角膜新生血管的研究进展进行综述.     

促红细胞生成素在眼部新生血管疾病发病中的作用

眼部新生血管是一组难治性致盲性眼病的共同临床表现.多种促新生血管因子是其发病的主要机制.促红细胞生成素(erythropoietin,EPO)不仅具有调节红细胞生成的作用,也是一种促新生血管因子,在生理和病理性血管形成过程中起重要作用.EPO在角膜新生血管、视网膜新生血管等形成过程中表达增加,在氧诱导的视网膜新生血管动物模型中,阻断EPO信号可以抑制新生血管形成.这些研究提示EPO在眼部新生血管疾病中起重要作用,有望成为治疗眼部新生血管的新靶点.     

血管内皮生长因子抑制剂治疗视网膜新生血管性疾病

视网膜新生血管性疾病是致盲的主要病因,早期预防、控制视网膜新生血管的发生发展显得尤为重要。目前,关于视网膜新生血管性疾病的确切发病机制尚不清楚,但对血管内皮生长因子(vascular endothelial growth factor,VEGF)在其形成过程中起关键作用已达成共识,现在已有多种VEGF抑制剂被用于治疗眼部新生血管性疾病。现将治疗视网膜新生血管性疾病的最新几种VEGF抑制剂作一综述。     

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。     

肝细胞生长因子与视网膜新生血管形成

视网膜新生血管形成可造成眼部多种组织成分的广泛损害,已成为世界范围的致盲性疾病.其发生及发展过程复杂,需要多种因素参与,包括多种生长因子的相互作用等.肝细胞生长因子（HGF）作为多效性生长因子,对新生血管形成的作用逐渐被认识.本文主要探讨HGF在视网膜新生血管发病机制中的作用以及与血管内皮生长因子（VEGF）的关系.     

肝细胞生长因子与视网膜新生血管形成

视网膜新生血管形成可造成眼部多种组织成分的广泛损害,已成为世界范围的致盲性疾病。其发生及发展过程复杂,需要多种因素参与,包括多种生长因子的相互作用等。肝细胞生长因子(HGF)作为多效性生长因子,对新生血管形成的作用逐渐被认识。本文主要探讨HGF在视网膜新生血管发病机制中的作用以及与血管内皮生长因子(VEGF)的关系。     

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。     

Bilateral choroidal osteoma with unilateral polypoidal choroidal vasculopathy treated with conbercept

Ischemic and neovascular diseases are one of the most difficult ocular diseases to deal with nowadays. Redundancy, poor visual acuity and decreased life quality are bothering patients and ophthalmologists for decades. After VEGF was found to be a primary factor in promoting retinal angiogenesis, intravitreal injection of anti-VEGF drugs has been the first-line treatment. Whereas, some patients are refractory to this therapy and problems of economic burden, local complications and adverse effects promote researches into other possible targets. The vasohibin (VASH) family is a newly-investigated factor in modulating ocular angiogenesis. The family includes VASH1 and VASH2, which show opposite effects of inhibiting and accelerating angiogenesis respectively. Positive results have been reported in cellular and animal experiments. With further researches, it can be a promising future target of treating ocular neovascular diseases.     

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。     

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.     

Diverse roles of macrophages in intraocular neovascular diseases: a review

Macrophages are involved in angiogenesis, and might also contribute to the pathogenesis of intraocular neovascular diseases. Recent studies indicated that macrophages exert different functions in the process of intraocular neovascularization, and the polarization of M1 and M2 phenotypes plays extremely essential roles in the diverse functions of macrophages. Moreover, a large number of cytokines released by macrophages not only participate in macrophage polarization, but also associate with retinal and choroidal neovascular diseases. Therefore, macrophage might be considered as a novel therapeutic target to the treatment of pathological neovascularization in the eye. This review mainly summarizes diverse roles of macrophages and discusses the possible mechanisms in retinal and choroidal neovascularization.     

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.     

Etiology, pathogenesis, and diagnosis of neovascular glaucoma

Neovascular glaucoma is defined as iris and/or anterior chamber angle neovascularization associated with increased intraocular pressure. It is a secondary glaucoma that is most frequently caused by severe retinal ischemia. The most common diseases responsible for the development of neovascular glaucoma are diabetic retinopathy, ischemic central retinal vein occlusion, and ocular ischemic syndrome. Uncommon causes include ocular radiation, ocular tumors, uveitis and other miscellaneous conditions. Vascular endothelial growth factor is an important and likely predominant agent involved in the pathogenesis of intraocular neovascularization and neovascular glaucoma. The evolution of clinical and histopathological changes from predisposing conditions to the occurrence of rubeosis iridis and neovascular glaucoma is divided into four stages: prerubeosis, preglaucoma, open angle glaucoma, and angle-closure glaucoma.     

Role of vascular endothelial growth factor in ocular angiogenesis

VEGF-A is a critical regulator of ocular angiogenesis and vascular permeability and is involved in the pathogenesis of several ocular diseases involving neovascularization or increased vascular permeability, such as neovascular AMD, diabetic ME, and diabetic retinopathy. Currently available therapies for neovascular AMD, such as laser photocoagulation, PDT with verteporfin, and pegaptanib sodium, slow visual loss but do not improve vision for most patients. In contrast, an emerging anti-VEGF agent, ranibizumab, improved vision in 25% to 34% of treated patients in one clinical trial, rather than slowing visual loss and is the first treatment for neovascular AMD to demonstrate visual improvement in a substantial number of patients. This represents a major advance in the treatment of ocular diseases involving neovascularization or increased vascular permeability and provides hope to patients with these debilitating diseases. Since the submission of this article, ranibizumab was approved by the FDA for the treatment of neovascular AMD.     

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.