巨噬细胞在小鼠氧诱导视网膜新生血管形成中的作用

目的　探讨巨噬细胞对小鼠氧诱导视网膜病变（ｏｘｙｇｅｎ-ｉｎｄｕｃｅｄｒｅｔｉｎｏｐａｔｈｙ,ＯＩＲ）形成的影响。方法　将新生Ｃ５７ＢＬ／６Ｊ小鼠随机分为３组,分别为常氧对照组、ＯＩＲ模型组以及清除巨噬细胞的ＯＩＲ组。将后两组小鼠于生后第７天（Ｐ７）至Ｐ１２置于体积分数（７５±２）％高氧氧箱中以诱导ＯＩＲ。清除巨噬细胞的ＯＩＲ组小鼠于Ｐ９、Ｐ１１、Ｐ１３和Ｐ１５接受腹腔注射氯膦酸二钠脂质体４次以清除全身单核-巨噬细胞,ＯＩＲ模型组小鼠则于上述４个时间点接受腹腔注射ＰＢＳ脂质体。三组小鼠均于Ｐ１７时取右眼行视网膜铺片和Ｌｅｃｔｉｎ染色,观察视网膜出血及血管生长情况;取左眼行视网膜切片和ＨＥ染色,观察视网膜组织病理学变化。结果　与常氧对照组相比,ＯＩＲ模型组小鼠视网膜存在出血现象,清除巨噬细胞的ＯＩＲ组出血有所减轻。ＯＩＲ模型组小鼠视网膜血管形态呈异常增殖的团簇状,走行迂曲,而清除巨噬细胞的ＯＩＲ组小鼠视网膜新生血管异常形态减轻。与ＯＩＲ模型组相比,清除巨噬细胞的ＯＩＲ小鼠视网膜无血管区及新生血管区面积均显著减小［（１７．１９±０．５８）％、（１０．３８±０．５３）％,ｔａ＝８．６８０,Ｐ＜０．０１;（４．６０±０．１５）％、（２．５１±０．１３）％,ｔｎ＝１０．８３,Ｐ＜０．０１］,突破内界膜新生血管内皮细胞核数目明显减少（１８．５０±０．８５、７．１７±０．４８;ｔ＝１１．６６,Ｐ＜０．０１）。结论　清除巨噬细胞可减轻小鼠ＯＩＲ严重程度,提示巨噬细胞对视网膜新生血管形成具有促进作用。     

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.     

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.     

巨噬细胞的异质性在视网膜新生血管中的作用

视网膜血管疾病是临床上一类病因复杂、机制尚不明确的致盲眼病，其主要的病理生理学特征是视网膜新生血管形成。大量的基础研究和临床证据证实，免疫相关巨噬细胞（macrophages，MФ）在视网膜新生血管形成中发挥着重要作用。MФ可分为经典活化的、促炎性的M1型和替代活化的、免疫抑制性的M2型，M2型MФ根据刺激信号和功能的不同又可分为M2a、M2b、M2c 3种。而MФ的不同亚型在视网膜新生血管形成发生发展中的作用还存在争议。因此，明确其不同亚型的具体作用，对深入理解视网膜新生血管形成性疾病的发病机制和临床治疗十分关键。（国际眼科纵览， 2018,  42:  119-124）     

精氨酸-谷氨酰胺在幼鼠早产儿视网膜病变模型中的应用(英文)

目的:观察精氨酸-谷氨酰胺(Arg-Gln)对早产儿视网膜病变动物模型视网膜新生血管的抑制作用。方法:48只7日龄的C57BL/6J新生鼠暴露在750mL/L高氧环境中5d,然后回到正常空气中建立早产儿视网膜病变的动物模型。在鼠龄12d时实验组(36只)新生鼠每天两次腹腔注射Arg-Gln(剂量分别为1.0,3.0,5.0g/kg,每组12只),连续注射5d;对照组(12只)每天两次腹腔注射PBS,连续5d。所有小鼠均于17d处死,视网膜铺片,ADP酶染色观察视网膜血管情况。HE染色,在光学显微镜下观察并计数突破视网膜内界膜的血管内皮细胞细胞核数目。Real-time RT-PCR方法测量每组视网膜VEGF mRNA水平。结果:与对照组相比,实验组以剂量依赖方式无灌注区面积和新生血管团逐渐减少;实验组中最大剂量组[5.0g/(kg·d)]突破内界膜的内皮细胞细胞核数目比对照组大约减少75%(P<0.01);实验组视网膜VEGF mRNA水平与对照组相比明显下降。结论:Arg-Gln能够有效抑制早产儿视网膜病变动物模型视网膜新生血管的生成,可能为临床提供一种预防和治疗早产儿视网膜病变安全有效的新方法。     

巨噬细胞极化在眼科疾病发生发展过程中的作用机制研究进展

巨噬细胞是单核吞噬细胞系统的主要细胞群,充当先天性免疫和适应性免疫的哨兵.在微环境信号作用下,巨噬细胞可被不同的激活物极化为不同功能的M1型、M2型巨噬细胞.巨噬细胞极化既可以发生在生理条件下,也可以发生在病理条件下,并贯穿疾病发生、发展以及转归的全过程.很多眼科疾病的病理过程都和巨噬细胞极化密切相关,巨噬细胞极化及炎...     

周细胞在新生血管性眼病中的作用研究进展

新生血管性眼病以病理性新生血管形成为病理特征,是威胁眼健康的主要疾病。近年来,各种新生血管性眼病发病率逐年提高,已成为严重的公共卫生问题,引起了广泛关注。病理性新生血管是多种细胞成分、多种病理因素互相包含、交互影响下形成的,单独干预其中一种因素往往很难达到理想治疗效果,因此需要更深入地研究新生血管的病理过程,探究新的调控新生血管的因子,以发现更有效的治疗方法。近年来研究发现,周细胞在多种新生血管性眼病的发生发展中起重要作用,针对周细胞采取干预措施将影响这些疾病的病理过程。本文将对新生血管性眼病中周细胞的具体作用以及调控周细胞的因素作出综述,为新生血管性眼病的治疗提供新的思路和方向。     

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.     

氧诱导的血管增生性视网膜病变小鼠模型

目的 建立可量化的血管增生性视网膜病变小鼠模型。方法 将鼠龄为7d的C57BL/6J幼鼠17只暴露于75％氧浓度环境下饲养持续5d,然后回到正常空气中饲养;17只同龄幼鼠置于正常空气环境中饲养作为对照。ADP酶法视网膜铺片了解视网膜血管的改变;用组织切片观察并计数突破视网膜内界膜的内皮细胞核数目;视网膜组织切片用CD31进行免疫组织化学染色。结果 持续高浓度氧使幼鼠视网膜血管收缩、分支闭塞、中央部可见灌注降低,相对低氧使视网膜血管扩张、增生。组织切片可见正常对照组平均每张切片突破内界膜内皮细胞核数目<1个,给氧组平均24个/切片,两组比较差别有显著性意义(P<0.01)。给氧组视网膜组织切片经用CD31抗体处理后显示内界膜玻璃体面细胞染色阳性。结论 该模型具有可重复性强、可定量研究的优点,是进行视网膜新生血管发生机制及药物干预的合适模型。     

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。     

Intravitreal Bevacizumab (Avastin) Treatment of Neovascular Glaucoma in Ocular Ischemic Syndrome

We report a case of ocular ischemic syndrome accompanied by neovascular glaucoma that was successfully treated with Bevacizumab. A 70-year-old male patient diagnosed with neovascular glaucoma of the left eye 3-4 years prior complained of continuous left eye pain and declining visual acuity despite receiving the latest treatment methods. At the time of admission the patient had no light perception in the left eye and his intraocular pressure was 30 mmHg. Anterior segment and fundus examinations revealed neovascularization of the iris and stenosis of the retinal vessel. Hypofluorescence of the choroid and retinal vessels was observed on fluorescence fundus angiography. Left internal carotid artery stenosis was observed on a brain MRI. Despite being treated with eye solution and oral medication, intraocular pressure was not controlled. After 7 days, we performed an intravitreal Bevacizumab 1.25 mg/0.05mL injection. One day after the intravitreal Bevacizumab injection, the neovascularization had nearly regressed and intraocular pressure was 30 mmHg. Intravitreal Bevacizumab injection produced regression of neovascularization and proved effective for treatment of neovascular glaucoma in this case of ocular ischemic syndrome.     

骨髓间充质干细胞治疗视网膜新生血管性疾病的研究进展

视网膜新生血管性疾病并非独立的一种眼病,常见于许多眼病中,如早产儿视网膜病变、糖尿病视网膜病变、年龄相关性黄斑变性、视网膜中央静脉阻塞和视网膜静脉周围炎等都会形成新生血管,是严重损害视力的病变。此类疾病丧失正常血管的结构和功能,引起病理性出血、渗出、水肿和视网膜脱离等病理性改变,是视力丧失的主要原因,已经成为世界范围的致盲性疾病。目前主要的治疗方法为针对病因进行激光封闭,或行玻璃体切除术,或是反复、多次玻璃体腔注射抗血管内皮生长因子,虽然短期效果好,但不能防止复发,目前仍没有长期有效的治疗方法。干细胞治疗的出现为此提供了潜在的替代疗法。本文将对骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)在视网膜新生血管疾病中的最新应用进展作一综述,展示其移植优势和良好的临床应用前景。     

Ang-2在高氧诱导新生鼠ROP动物模型中的表达及意义

目的：研究Ang-2在高氧诱导新生鼠ROP动物模型中的表达,探讨Ang-2在视网膜新生血管形成中的作用。方法60只新生SD大鼠,随机分为高氧诱导组和正常对照组,将氧诱导组小鼠置于密闭容器中饲养,连接氧浓度测量仪,保持氧箱内氧浓度为75±2%,5d后将幼鼠取出置于常氧环境中饲养,正常对照组幼鼠置于普通空气中饲养。两组幼鼠均于出生后17d被处死,行眼球病理切片Ang-2免疫组织化学染色,了解Ang-2在视网膜新生血管的形成中的作用。结果高氧诱导组幼鼠生后17天视网膜新生血管和Ang-2的表达达高峰。P17d高氧诱导组幼鼠突破内界膜血管内皮细胞核数目（34.78±4.38）明显高于正常对照组（1.56±1.64）,两组比较差异有统计学意义（＜0.001）;P17天高氧诱导组幼鼠Ang-2表达明显高于正常对照组,其平均光密度值（OD值）分别为（117.25±10.67）和（83.29±9.15）,两组比较差异有显著性（＜0.001）。结论高氧诱导组幼鼠视网膜新生血管的形成同Ang-2的表达变化相一致,提示Ang-2在高氧诱导视网膜新生血管的形成中起一定作用。     

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)     

BIGH3基因在角膜疾病及糖尿病视网膜病变中的研究新进展

BIGH3基因在眼部疾病中起重要作用。一方面,与角膜疾病的发生息息相关,BIGH3基因可以抑制角膜新生血管形成,导致角膜营养不良,参与圆锥角膜形成; 另一方面,可以导致糖尿病视网膜病变中新生血管的生成,有最新实验证明,巨噬细胞分泌的TGFβ可以促进BIGH3 mRNA和BIGH3蛋白的表达,并促进视网膜内皮细胞和周细胞凋亡,从而导致糖尿病视网膜病变新生血管的形成。本文将从如上几个方面阐述BIGH3基因在眼部疾病研究的新进展。     

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。     

Metabolomics Analyses of Mouse Retinas in Oxygen-Induced Retinopathy

PurposeRetinal neovascularization is a severe pathological process leading to irreversible blindness. This study aims to identify the altered metabolites and their related pathways that are involved in retinal neovascularization.MethodsTo reveal the global metabolomic profile change in the retinal neovascularization process, an untargeted metabolomics analysis of oxygen-induced retinopathy (OIR) mice retinas was carried out first, followed by the validation of amino acids and their derivatives through a targeted metabolomics analysis. The involved pathways were predicted by bioinformatic analysis.ResultsBy untargeted metabolomics, a total of 58 and 49 metabolites altered significantly in OIR retinas under cationic and anionic modes, respectively. By bioinformatics analysis, “ABC transporters,” “central carbon metabolism in cancer.” and “alanine, aspartate, and glutamate metabolism” were the most enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with the changed metabolites. By targeted metabolomics, no significant change was found in the assessed amino acids and their derivatives at postnatal day (P) 12, whereas significantly altered amino acids and their derivatives were recognized at P13, P17, and P42 in OIR retinas.ConclusionsThe metabolomic profile was significantly altered in the neovascularized retinas. In particular, numerous amino acids and their derivatives were significantly changed in OIR retinas. These altered metabolites, together with their associated pathways, might be involved in the pathogenesis of retinal neovascular diseases.     

Primate model of neovascular glaucoma

Iris neovascularization has been reproducibly created in cynomolgus monkey eyes by argon laser occlusion of retinal veins. Pre-treatment of the eyes with lensectomy and vitrectomy (before the retinal vein occlusion) led to a more rampant development of the iris neovascularization in all eyes, as well as development of neovascular angle closure glaucoma in two of the 12 eyes. Histopathologic examination confirmed the finding of neovascular angle closure. This primate model may allow further investigation into the causes and therapy of neovascular glaucoma.