内皮抑素与眼部新生血管

眼部新生血管导致眼结构和功能的破坏,造成严重的视功能损害,是当前最难解决的眼科难题之一。内皮抑制素(endostatin,ES)是目前公认的最强的血管生成抑制因子之一,已经用于抑制眼部新生血管的实验研究,表明内皮抑制素具有强大的抗眼部新生血管作用。本文就内皮抑素的结构、功能及与眼部新生血管的相关研究进行综述。     

血管生成抑素、K-5和内皮抑素抑制眼新生血管的研究进展

血管生成抑素、K5和内皮抑素均是内源性新生血管抑制因子,结构上分别是纤维蛋白溶酶原和胶原ⅩⅧ的酶解片段。基因治疗眼新生血管方面的研究不断取得进展,本文对其进行了综述。     

血管抑素抑制大鼠角膜新生血管的研究

目的研究血管抑素（AS）对大鼠角膜碱烧伤后新生血管的抑制作用。方法120只Wistar大鼠制作碱烧伤角膜新生血管（CNV）模型,随机分为4组,分别为2.5μgAS组、5μgAS组、地塞米松组、生理盐水组,每组30只。分别给予2.5μg/0.1mLAS、5μg/0.1mLAS、0.1mg/0.1mL地塞米松、生理盐水各0.1mL,球结膜下注射,隔日1次,共4次。在大鼠角膜碱烧伤后不同时间裂隙灯下观察大鼠角膜混浊度,计算新生血管面积,分析角膜组织病理切片。结果2.5μgAS组、5μgAS组及地塞米松组在第7、10、14天较生理盐水组角膜混浊程度轻,差异均有统计学意义（P〈0.05）;2.5μgAS组、5μgAS组及地塞米松组在碱烧伤后第3天起各时间点新生血管面积小于生理盐水组,差异均有统计学意义（P〈0.05）。结论AS能有效抑制大鼠角膜碱烧伤后CNV的形成。     

血管能抑素抑制新生血管生成的研究进展

血管能抑素是最新发现的一种内源性血管抑制因子,来源于Ⅳ型胶原.实验证明其在体外能显著抑制血管内皮细胞的增生和迁移,诱导其凋亡,在体内能抑制肿瘤新生血管生成.血管能抑素作为抗血管生成治疗的新策略,在眼科基因治疗方面有很好的应用前景,尤其是视网膜新生血管.本文就血管能抑素的发现、命名、生物学特性、作用机制及在眼科应用前景作一综述.     

内皮抑素与眼内新生血管

内皮抑素是迄今发现的最强的血管生成抑制因子,它能抑制内皮细胞增生和迁移,诱导其凋亡,从而抑制新生血管的形成,它已成为治疗眼内新生血管疾病的有潜力的一种新药。本文就内皮抑素的结构、功能及其对眼内新生血管疾病的基因治疗进展作一综述。     

重组人血管内皮抑素对脉络膜新生血管的抑制作用

目的 探讨重组人血管内皮抑素对半导体激光诱导的Brown Norway大鼠脉络膜新生血管(choroidal neovascuIariza-tion,CNV)的抑制作用.方法 取雄性大鼠30只(60眼),大鼠双眼眼底采用半导体激光光凝建立CNV模型,随机分为3组:实验组、生理盐水组及空白对照组,每组10只(20眼).实验组玻璃体内注射重组人血管内皮抑素20 μL(5g·L-1),每2d注射1次,共注射5次;生理盐水组玻璃体内注射生理盐水20μL,每2d注射1次,共注射5次;空白对照组光凝后不做处理,观察期为14d.观察术后13d各组大鼠荧光素渗漏情况,术后14d光镜下观察组织细胞学变化,免疫组织化学检测CD105的表达,以及应用激光共聚焦显微镜下脉络膜血管平铺法测量各组CNV面积.结果 FFA显示实验组严重渗漏发生率明显低于生理盐水组和空白对照组;实验组光镜下光凝部位新生血管和内皮细胞数明显低于对照组;CD105的表达实验组明显低于生理盐水组和空白对照组;激光共聚焦显微镜下CNV定量分析显示实验组CNV面积(17352±1321)μm2小于生理盐水组(23043±1424)μm2和空白对照组(25937±1744)μm2,其差异具有显著统计学意义(F=342.4,P＜0.001).结论 重组人血管内皮抑素(恩度)可以有效抑制动物模型的CNV形成,为治疗CNV提供了一种新的可能途径.     

血管抑素对角膜新生血管和VEGF表达的作用

目的:探讨血管抑素(angiostatin,AS)对鼠碱烧伤角膜新生血管(corneal neovascularization,CNV)及血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)表达的作用,探讨 AS对CNV的作用及机制。方法:SD大鼠105只随机分为正常对照组(5只)、生理盐水组、地塞米松组、AS1组、AS2组(各25只),除正常组外,实验各组制作左眼碱烧伤CNV模型,分别予生理盐水、1g/L地塞米松液、10μg/mLAS液、20μg/mLAS液点眼,4次/d,于碱烧伤后1,3,7,14,21d运用裂隙灯、免疫组织化学方法观察新生血管长度及面积、VEGF的表达。结果:AS治疗组碱烧伤后第3d起各时间点CNV面积均明显小于盐水组(P<0.05)。碱烧伤后各时间点AS治疗组VEGF表达量均明显少于盐水组(P<0.05)。结论:AS能显著抑制碱烧伤CNV,可能与其抑制VEGF的表达有关。     

血管内皮抑素对眼内新生血管抑制的展望

血管内皮抑素(endostatin,ES)具有显著的特异性抑制血管内皮细胞生长的作用,为新生血管的治疗提供了新的方向。我国首次将血管内皮抑素研制成具有自主知识产权的国家一类新药Endostar(中文名恩度,YH-16)。目前血管内皮抑素在防治眼部新生血管性疾病方面已取得一些可喜的成就,我们就血管内皮抑素对眼内新生血管的治疗作用和治疗眼部新生血管性疾病的研究进展做一综述。     

改良内皮抑素与眼部新生血管的研究进展(英文)

内皮抑素是一种强有力的内源性血管生成抑制因子。它抑制血管内皮细胞的增生,迁移,且无毒性、无耐药性。内皮抑素在体外不稳定,需长期大剂量用药,如何提高内皮抑素生物活性是当今一个热门话题。内皮抑素可以通过化学共价修饰或基因突变改变其结构,提高其稳定性与抑制新生血管活性。我们旨在探讨改良内皮抑素与眼部新生血管的研究进展,并讨论改良内皮抑素的优越性。研究改良内皮抑素也有助于我们了解内皮抑素作用的分子机制.改良内皮抑素有望作为一种新的血管生成抑制剂应用于临床,从而取代内皮抑素。     

血管抑素防治眼内新生血管形成

眼内新生血管形成是老年性黄斑变性、糖尿病性视网膜病变和视网膜静脉阻塞等疾病共有的病理性改变。近年发现的血管抑素，具有特异性抑制内皮细胞增生的作用，据报道其在肿瘤的抗血管治疗中已进入临床试验阶段。本综述了国外学关于血管抑素在眼内新生血管治疗方面的研究进展。     

MicroRNA及其在眼科领域的研究进展

MicroRNAs是一组可负性调控基因表达的非编码蛋白质的短序列RNA,参与调节细胞的生长发育、分化、增殖、凋亡等重要的生理过程.它们主要通过降解mRNA或抑制靶基因的翻译发挥调节作用.目前已发现有400多种MicroRNAs在人类基因组中表达.越来越多的研究表明很多特定的MicroRNAs在眼部很多组织中包括角膜、晶状体、视网膜中均有表达.本文就MicroRNAs的来源、结构、功能、在眼部的表达及未来作为治疗眼部疾病一种可能手段的前景进行综述.(中华眼科杂志,2009,45:280-284)     

Applications of liposomes in ophthalmology

This review outlines the applications of liposomal formulations in ophthalmology. In ophthalmology, liposomes have been used to treat disorders of both the anterior and posterior segments. These include dry eyes, keratitis, corneal transplant rejection, uveitis, endophthalmitis, and proliferative vitreoretinopathy. Liposomes also have shown promise as vectors for genetic transfection and monoclonal antibody-directed vehicles. Furthermore, heat-activated liposomes have spurred research in focal laser and heat-induced release of liposomal drugs and dyes for selective drug delivery. These techniques have been useful in selective tumor and neovascular vessel occlusion, angiography, and retinal and choroidal blood-flow studies. Although verteporfin is the only liposomal drug currently approved for use in the eye, the benefits of liposomes will likely be applied widely in all treatment, diagnostic, and research aspects of ophthalmology in the future.     

关注和跟踪表观遗传研究在眼科疾病诊治中的应用

不涉及修改基因编码序列的、可遗传的基因表达变化称为表观遗传改变,眼科表观遗传学是当前生物医学研究的热点之一.表观遗传机制主要包括DNA甲基化、组蛋白修饰、染色质重排及非编码RNA.异常的DNA甲基化和组蛋白修饰与许多年龄相关性疾病密切关联,如癌症、自身免疫性疾病和其他疾病.近年来,表观遗传对眼科疾病发生和发展的调控机制及其在治疗中的作用日益引起研究者的关注,不仅加深了人们对相关眼病发病机制的理解,而且由于表观遗传性改变是可逆的,因此对与相关眼病有关的基因标志进行修饰也为这些疾病的预防、早期诊断和治疗提供了新的思路.我们讨论眼科表观遗传学的机制及表观遗传改变在眼病发生和发展过程中的作用,希望眼科研究人员重视基因表达改变与环境因素的相互作用及其对眼部发育和眼部疾病发病过程的影响,更重要的是应将这些研究成果更好地用于眼科疾病的预防和治疗.     

血管抑素玻璃体注射对糖尿病大鼠视网膜及虹膜血管渗漏的影响

目的 探讨血管抑素（Angiostatin）玻璃体腔注射对糖尿病大鼠视网膜、虹膜血管渗漏性的影响及其机理。方法 Brown Norway大鼠48只。静脉注射链唑霉素（Streptozotocin，STZ）建立糖尿病模型，随机分为3组（每组糖尿病鼠与正常鼠各8只）。甲组：右眼玻璃体腔注射磷酸盐缓冲生理盐水（Phosphate Buffered Saline，PBS）5山，左眼不注射；乙组、丙组：右眼玻璃体腔注射血管抑素7．5μg／5μl，左眼注射等量PBS；甲、乙组用埃文斯蓝微血管渗透性检测法检测视网膜和虹膜的血管渗透性。丙组用Western blot免疫印迹分析法检测视网膜血管内皮生长因子（Vascular Endothelial Growth Factor，VEGF）的表达。结果 糖尿病鼠较正常鼠的视网膜（P〈0．01）和虹膜（P〈0．05）的血管渗透性增加；糖尿病鼠血管抑素注射眼与对侧PBS注射眼相比，视网膜（P〈0．01）和虹膜（P〈0．05）血管渗透性降低；正常鼠注射血管抑素眼与对侧注射PBS眼相比，视网膜和虹膜血管渗透性无明显改变（P〉0．05）Western blot显示血管抑素显著降低了糖尿病鼠视网膜的VEGF水平，但对正常鼠无影响。结论 血管抑素可明显降低糖尿病鼠视网膜、虹膜血管渗透性，但对正常鼠影响不明显。血管抑素可下调糖尿病鼠视网膜VEGF的表达从而阻断其血管渗漏。因此预测血管抑素对糖尿病黄斑水肿、黄斑囊样水肿、葡萄膜炎等血管渗漏性疾病可能具有潜在的治疗价值。     

Applications of nanoparticles in ophthalmology

Nanocarriers, such as nanoparticles, have the capacity to deliver ocular drugs to specific target sites and hold promise to revolutionize the therapy of many eye diseases. Results to date strongly suggest that ocular medicine will benefit enormously from the use of this nanometric scale technology. One of the most important handicaps of the eye as a target organ for drugs is the presence of several barriers that impede direct and systemic drug access to the specific site of action. Superficial barriers include the ocular surface epithelium and the tear film, and internal barriers include the blood–aqueous and blood–retina barriers. Topical application is the preferred route for most drugs, even when the target tissues are at the back part of the eye where intraocular injections are currently the most common route of administration. Direct administration using any of these two routes faces many problems related to drug bioavailability, including side effects and repeated uncomfortable treatments to achieve therapeutic drug levels. In this regard, the advantages of using nanoparticles include improved topical passage of large, poorly water-soluble molecules such as glucocorticoid drugs or cyclosporine for immune-related, vision-threatening diseases. Other large and unstable molecules, such as nucleic acids, delivered using nanoparticles offer promising results for gene transfer therapy in severe retinal diseases. Also, nanoparticle-mediated drug delivery increases the contact time of the administered drug with its target tissue, such as in the case of brimonidine, one of the standard treatments for glaucoma, or corticosteroids used to treat autoimmune uveitis, a severe intraocular inflammatory process. In addition, nanocarriers permit the non-steroidal anti-inflammatory drug indomethacin to reach inner eye structures using the transmucosal route. Finally, nanoparticles allow the possibility of targeted delivery to reach specific types of cancer, such as melanoma, leaving normal cells untouched.This review summarizes experimental results from our group and others since the beginnings of nanocarrier technology to deliver drugs to different locations in the eye. Also, it explores the future possibilities of nanoparticles not only as drug delivery systems but also as aides for diagnostic purposes.     

血管抑素对视网膜微血管内皮细胞的细胞外 信号调节激酶水平的影响

目的观察血管抑素对体外培养的鼠视网膜微血管内皮细胞的细胞外信号调节激酶(ERK-1)活性的影响。方法利用l-lysine 耦联的sepharose 4B亲和层析柱从血浆中分离和纯化血管抑素。 原代培养鼠视网膜微血管内皮细胞分为4组:对照组,血管内皮因子(VEGF)10 ng/ml组, 血管抑素130 μg/ml组，VEGF(10 ng/ml)+血管抑素(130 μg/ml)组，Western-blotting检测血管抑素对血管内皮因子刺激后1、2、5、10、15、30 min的视网膜微血管内皮细胞ERK-1水平的影响。结果与对照组相比，经血管抑素处理后1 min，ERK-1水平开始下降，10 min时下降最为显著，30 min后对照组与血管抑素组ERK水平没有显著区别。VEGF刺激后，鼠视网膜微血管内皮细胞中ERK 1被迅速激活，5 min后达到高峰，VEGF组ERK水平较对照组提高了210%（P＜0.05）；30 min后, VEGF组ERK水平与对照组比较，差异无统计学意义（P＞0.05）。而血管抑素能使ERK-1的表达量降低11.9%(1 min)、17.9%(2 min)、387%(5 min)、49.3%(10 min) （P＜0.05）、27.9%(15 min)、1.12%(30 min)。结论血管抑素在体外能有效的阻断VEGF由细胞外向细胞核传导的信号通路。(中华眼底病杂志,2005,21:170-173)     

儿童眼病筛查的方法及其应用价值研究

目的研究对儿童眼病进行初步筛查的实用、便利的方法和工具。方法利用红光反射试验 (Bruckner Test)原理,使用特殊儿童验光仪,对门诊儿童眼科病人分别进行常规观察、眼病筛查检查,结合临床验证眼病筛查方法的使用价值。比较各种方法的效果。结果对于几种常见儿童眼病,通过典型病例观察,总结出可以应用眼病筛查实践的、特异性儿童眼病眼部图像改变。就筛查的有效性分析,PR-2000筛查方法组敏感性为99． 8％,特异性为97．9％。就实用性分析,PR-2000筛查方法组的阳性预测价值为94．1％,阴性预测价值为99．9％。结论儿童眼病筛查是一种简单快捷的眼病筛查手段,能够早期发现许多儿童眼部异常。可以用作儿童眼科的常备工具,也可以用于初级儿童眼保健。     

Applications of SMILE-extracted lenticules in ophthalmology

AIM: To review recent innovations, challenges, and applications of small incision lenticule extraction (SMILE) extracted lenticule for treating ocular disorders. METHODS: A literature review was performed in the PubMed database, which was last updated on 30 December 2021. There was no limit regarding language. The authors evaluated the reference lists of the collected papers to find any relevant research. RESULTS: Due to the simplicity and accuracy of modern femtosecond lasers and the extensive development of SMILE surgery, many healthy human corneal stromal lenticules were extracted during surgery, motivating some professionals to investigate the SMILE lenticule reusability in different ocular disorders. In addition, new approaches had been developed to preserve, modify, and bioengineer the corneal stroma, leading to the optimal use of discarded byproducts such as lenticules from SMILE surgery. The lenticules can be effectively re-implanted into the autologous or allogenic corneas of human subjects to treat refractive errors, corneal ectasia, and corneal perforation and serve as a patch graft for glaucoma drainage devices with better cosmetic outcomes. CONCLUSION: SMILE-extracted lenticules could be a viable alternative to human donor corneal tissue.     

Applications of three-dimensional printing in ophthalmology

Three-dimensional (3D) printing is increasingly used to produce customized objects and is a promising alternative to traditional manufacturing methods in diverse fields, such as dentistry and orthopedics. Already in use in other medical specialties, adoption in ophthalmology has been limited to date. This review aims to provide an overview of 3D printing technology with respect to current and potential applications in ophthalmic practice.Medline, Embase, and Internet searches were performed with “3D printing,” “ophthalmology,” “dentistry,” “orthopaedics” and their synonyms used as main search terms. In addition, search terms related to clinical applications such as “surgery” and “implant” were employed.3D printing has multiple applications in ophthalmology, including in diagnosis, surgery, prosthetics, medications, and medical education. Within the past decade, researchers have produced 3D printed models of objects such as implants, prostheses, anatomical models and surgical simulators. Further development is necessary to generate optimal biomaterials for various applications, and the quality and long-term performance of 3D models needs to be validated.