内皮祖细胞与新生血管性眼病的关系

内皮祖细胞(EPC)是一种成年个体骨髓中的前体细胞,它具有良好的增生潜能.EPC不仅参与受损血管内皮修复,而且参与病理性新生血管形成.新生血管性眼病是因局部缺血、缺氧导致的眼部新生血管形成为主要病理改变的一类疾病,包括糖尿病视网膜病变、老年性黄斑变性、早产儿视网膜病变及角膜新生血管等.通过研究EPC与常见新生血管性眼病的关系对于深入了解眼部新生血管的发病机制及治疗具有重要的意义.     

内皮祖细胞与新生血管性眼病的关系

内皮祖细胞(EPC)是一种成年个体骨髓中的前体细胞,它具有良好的增生潜能.EPC不仅参与受损血管内皮修复,而且参与病理性新生血管形成.新生血管性眼病是因局部缺血、缺氧导致的眼部新生血管形成为主要病理改变的一类疾病,包括糖尿病视网膜病变、老年性黄斑变性、早产儿视网膜病变及角膜新生血管等.通过研究EPC与常见新生血管性眼病的关系对于深入了解眼部新生血管的发病机制及治疗具有重要的意义.     

内皮祖细胞与新生血管性眼病的关系

内皮祖细胞(EPC)是一种成年个体骨髓中的前体细胞,它具有良好的增生潜能.EPC不仅参与受损血管内皮修复,而且参与病理性新生血管形成.新生血管性眼病是因局部缺血、缺氧导致的眼部新生血管形成为主要病理改变的一类疾病,包括糖尿病视网膜病变、老年性黄斑变性、早产儿视网膜病变及角膜新生血管等.通过研究EPC与常见新生血管性眼病的关系对于深入了解眼部新生血管的发病机制及治疗具有重要的意义.     

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。     

Bevacizumab在眼表疾病中的应用

眼表疾病是临床常见的致盲眼病,特别是角膜新生血管性眼病因其发病机制非常复杂,治疗棘手而成为眼科新研究领域一大难点和热点。Bevacizumab给药靶向阻断血管内皮生长因子及其受体,有效抑制新生血管生长,其抗淋巴血管性、抗纤维性有望成为角膜移植术后免疫排斥反应、LASIK术前常规及预防用药,现综述如下。     

眼部新生血管形成机制及其抑制剂研究进展

新生血管在大部分眼病的发生发展过程中均起着重要作用 ,并常导致严重视力下降 ,甚至丧失 ,如老年黄斑变性、糖尿病视网膜病变、新生血管性青光眼、碱烧伤后角膜新生血管等目前均无有效的治疗方法。为了控制这些疾病的发生、发展 ,近年来科学家们对眼部新生血管进行了大量研究 ,本文对目前眼部新生血管的形成机制及其抑制剂的研究状况作一综述。一、眼部新生血管的形成过程血管内皮细胞沐浴在血管形成促进因子和抑制因子的海洋中 ,这些内源性血管形成促进因子和抑制因子在正常情况下处于复杂而精细的平衡状态 ,使得眼部的血管处于非增殖的静…     

眼部新生血管发生发展的研究进展

不同眼病过程中，新生血管可出现在角膜、睫状体、虹膜、脉络膜、玻璃体及视网膜等，形成角膜血管翳、新生血管性青光眼、增殖型糖尿病性视网膜病变（ＰＤＲ）和视网膜下新生血管膜（ＳＲＮＭ）等。自从１９８０年Ｇｌａｓｅｒ等从人、牛和猫等哺乳类动物的视网膜浸出物中...     

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。     

眼内新生血管与细胞因子

新生血管性眼病是眼科的难治性疾病和重要的致盲原因。新生血管的形成是许多细胞因子参与并相互作用的一个复杂过程,大量的研究表明新生血管形成与血管生成因子和血管生成抑制因子之间的失衡有关,促血管生成因子如生长因子、炎性细胞因子、瘦素等水平的提高和/或血管生成抑制因子如色素上皮细胞衍生因子、生长抑素等的减少将导致眼内新生血管的形成、发展,但其分子机制尚待阐明。     

干扰素诱导蛋白-10与新生血管性眼病关系的研究进展

干扰素诱导蛋白-10(IP-10)属于EL-CXC类趋化因子,是目前研究较多的一个分子,其唯一的受体是CXCR3.IP-10与其受体特异性结合后,可以发挥抑制新生血管的形成及抗纤维化的作用,该生物学功能也参与新生血管性眼病的发病进程.研究证实,IP-10与亚临床慢性炎症紧密相关,参与年龄相关性黄斑变性(AMD)的发病过程,可能成为一项AMD发病的临床检测指标;表达于脉络膜新生血管内皮细胞上的IP-10/CXCR3信号通路有抑制脉络膜新生血管的作用;此外,IP-10在AMD患眼病灶内的高表达可能与血管内皮生长因子表达升高,反馈性诱导负性调控因子(IP-10等)生成相关.IP-10参与糖尿病视网膜病变(DR)的发病过程中,可用于临床检测DR病情的严重程度及预后评估的新指标,以及可能具有使增生性DR(PDR)患者活动期新生血管生成中止、促进新生血管纤维化的作用,从而抑制PDR的发展.IP-10可通过下调炎症细胞促血管生成因子表达的间接作用以及通过抑制血管内皮细胞迁移和管腔形成的作用直接减少角膜新生血管的生成.IP-10可能参与早产儿视网膜病变和脉络膜息肉样病变的发病过程.鉴于其独特的生物学功能,有望运用IP-10作为靶点进行临床靶向治疗达到抑制新生血管性眼病的目的.本文就近年来IP-10与几种常见新生血管性眼病关系的研究进展进行综述.     

Color Doppler imaging of choroidal circulation in patients with asymmetric age-related macular degeneration

We aimed at evaluating the possible role of choroidal perfusion abnormalities in the development of choroidal neovascularisation (CNV) in patients with age-related macular degeneration (AMD). Twenty-six patients who had non-exudative AMD in the first eye and CNV secondary to AMD in the fellow eye were enrolled. Blood flow velocities, vessel pulsatilities and resistivities were measured from ophthalmic artery, nasal and temporal posterior ciliary arteries using colour Doppler imaging. Systolic and diastolic velocities were lower in eyes with CNV for all vessels, except for the systolic velocity of the nasal posterior ciliary artery (p >0.05). Pulsatility and resistivity indices were higher in eyes with CNV for all vessels. This difference was statistically significant for the resistivity index of the nasal and temporal posterior ciliary arteries (p = 0.032 and p = 0.021, respectively) and the pulsatility index of the nasal posterior ciliary artery (p = 0.035). We have shown that in patients with AMD choroidal blood flow is more impaired in the eyes with CNV than in the fellow eyes.     

Histological findings of a surgically excised myopic choroidal neovascular membrane after photodynamic therapy

Background The authors describe a myopic choroidal neovascular membrane excised 4 months after photodynamic therapy (PDT).Methods A 68-year-old woman with classic choroidal neovascularization (CNV) due to pathologic myopia underwent PDT with verteporfin in the left eye. Four months after treatment a full-thickness macular hole was diagnosed in the same eye and the patient underwent vitrectomy with submacular membranectomy. The subfoveal membrane was studied by light microscopy and immunohistochemical techniques.Results Light microscopy showed a thin fibrovascular membrane covered by residual retinal pigment epithelium. The membrane contained homogeneous matrix with small collagen bundles, fibroblasts and small blood vessels. The distribution of blood vessels was nonuniform: extravasated red blood cells, macrophages and other inflammatory elements were not present in the fibrous matrix. Endothelial cells were highlighted by CD34 immunostaining and did not show any significant alteration. There was no evidence of inflammatory cells or thrombosis inside vascular lumina.Conclusions Histologic examination of the neovascular membrane showed features similar to those of surgically excised myopic CNV without PDT treatment. Our findings suggest that PDT-induced occlusion is temporary. Fluorescein leakage from CNV after a single PDT treatment can be considered as an sign of blood vessel regrowth or recanalization indicating that multiple treatments are necessary.     

A new model of experimental subretinal neovascularization in the rabbit

Existing animal models of choroidal neovascularization (CNV) present several problems: they are hard to reproduce, they are inefficient, and the CNV created is not sustainable. The purpose of this study is to develop a highly efficient, reliable, sustainable rabbit model of CNV to facilitate the study of anti-angiogenic and anti-proliferative therapies for ocular diseases. Twenty-two pigmented rabbits were used in this study. Eleven rabbits received subretinal injections of either 10 microl of Matrigel with 500 ng of vascular endothelial growth factor (VEGF) or 20 microl of Matrigel with 750 ng of VEGF; eight rabbits received subretinal injections of either 10 or 20 microl of Matrigel only; three rabbits used as controls received subretinal injections of 20 microl phosphate-buffered saline (PBS) alone. Fundus photography, fluorescein angiography, optical coherence tomography, and histologic examinations were performed 1, 2, 4, and 9 weeks after injection. All experimental eyes showed angiographic leakage within this localized area 1 week after injection. The amount of leakage usually increased at weeks 2 and 4 and, in most cases, persisted at week 9. Control eyes demonstrated no leakage at any time point. Optical coherence tomography of treated eyes showed subretinal fluid and the presence of a lesion, possibly vascular or fibrotic, at the site of the leakage. Histologic analysis confirmed the presence of new subretinal blood vessels in the areas of Matrigel deposit. In conclusion, this novel method provides a highly reproducible, reliable, and sustainable rabbit model of experimental choroidal neovascularization. Such a model may prove useful for screening new anti-angiogenic therapies in a larger animal eye.     

Age as an independent risk factor for severity of experimental choroidal neovascularization

PURPOSE: For many vascular diseases, aging appears to be an independent risk factor for severity of vascular complications, and blood vessels of aged individuals often demonstrate exaggerated repair responses to injury. This study was undertaken to determine the influence of aging on the severity of neovascularization in a mouse model of laser-induced choroidal neovascularization (CNV). METHODS: CNV was induced in young (2-month-old) and aged (16-month-old) C57BL/6 mice by making four separate choroidal burns in each eye with a diode red laser (650 nm). At 1, 2, and 4 weeks, the left eyes were removed for histopathology, and the right eyes were removed for flatmount analysis of CNV surface area, vascularity, and cellularity. RESULTS: Aged mice demonstrated a much larger area of CNV than did young mice (3.81 +/- 1.28 vs. 1.36 +/- 0.99 disc areas, P < 0.001) at 2 weeks, when the lesions showed maximum growth. Aged mice also demonstrated higher ratios for vascularity and cellularity of the CNV (1.34 +/- 0.06 vs. 1.03 +/- 0.11, P < 0.0001 and 4.06 +/- 1.19 vs. 1.91 +/- 0.81, P < 0.002 at 2 weeks, respectively). Histopathology revealed that CNV in older eyes was larger, thicker, and more cellular than in young eyes. CONCLUSIONS: In mice, age is associated with more severe CNV, defined as larger surface area, greater vascularity, and greater cellularity. Age-related systemic susceptibility factors, independent of local changes in the retina, may contribute to the greater severity of CNV in older than in younger individuals.     

血管内皮生长因子与病理性脉络膜新生血管

脉络膜新生血管(choroidal neovascularization,CNV)是造成许多眼底疾病和视力严重下降的主要原因。而血管内皮生长因子(vascular endothelial growth factor,VEGF)与CNV的形成密切相关,VEGF的过度表达将导致CNV形成。抗VEGF治疗能有效抑制CNV形成,从而达到治疗效果。本文就VEGF在眼内的分布及其在病理性CNV生成中的表达,和病理性CNV抗VEGF治疗的研究现状做一综述。     

血管内皮生长因子抑制剂在角膜新生血管治疗中的研究进展

正常角膜是无血管、完全透明的组织,是眼部重要的屈光介质,但许多眼部疾病均可破坏抗血管生成因子与促血管生成因子之间的平衡,导致病理性角膜新生血管(CNV)的形成.大量研究表明,CNV的形成与血管内皮生长因子(VEGF)信号通路的激活密切相关.通过多靶点多途径阻断该信号通路可以有效抑制新生血管的形成,为CNV的治疗带来了希望.目前,针对新生血管性眼病的新型靶向治疗策略主要包括VEGF抑制剂和以微小RNA(miRNA)为核心的基因治疗,前者主要包括抗VEGF单克隆抗体、核酸适体、VEGFtrap、VEGF受体(VEGFR)酪氨酸激酶抑制剂等.本文将对具有代表性的抗VEGF药物和基因治疗的作用机制、用药疗效、药物安全性及研究现状进行综述.     

Combining surgical ablation of retinal inflow and outflow vessels with photodynamic therapy for retinal angiomatous proliferation

PURPOSE: To evaluate short-term efficacy of combining surgical ablation of retinal inflow and outflow vessels and photodynamic therapy (PDT) for stage 3 retinal angiomatous proliferation (RAP). DESIGN: Prospective interventional case series. METHODS: Five eyes (five patients) underwent surgical ablation of inflow and outflow vessels and PDT for stage 3 RAP. RESULTS: Inflow and outflow vessels were ablated in four eyes, and only inflow was ablated in one eye. In four eyes starting PDT within six weeks of surgical ablation, choroidal neovascularization (CNV) disappeared or shrank after one PDT session (three months follow-up). However, CNV enlarged again in three of the four (final follow-up) because of reperfusion from newly formed inflow vessels. In one eye starting PDT seven months after ablation, a new retinal inflow vessel feeding the CNV appeared by the time of the first PDT session. The CNV continued to expand, despite two PDT sessions. CONCLUSIONS: Combining surgical ablation and PDT was not useful on account of a high frequency of reperfusion from retinal inflow vessels.     

Clinical course and treatment outcomes of Sorsby fundus dystrophy

PURPOSE: To analyze the natural history of Sorsby fundus dystrophy and the effect of various treatment methods for choroidal neovascularization (CNV) in this dystrophy. DESIGN: Historical cohort study. METHODS: A cohort of 42 patients with the Ser181 Cys TIMP3 mutation were identified from the electronic database of genetic retinal diseases in Moorfields Eye Hospital. Retrospective analyses of case records were carried out. Serial best-corrected visual acuity, fundus findings, age at onset of CNV, initial location of CNV, time taken for CNV to progress to subfoveal location, and the interval between development of CNV in the first and second eye were recorded. The time taken for CNV to recur to a subfoveal location in patients in whom argon laser photocoagulation was carried out for extrafoveal CNV also was documented. In cases where photodynamic therapy (PDT) was carried out for subfoveal CNV, the visual outcome, number of PDT treatments, and progression of lesion size were noted. RESULTS: The median age at onset of CNV in the first eye was 46.1 years and in the second eye was 50.3 years. The mean interval between the development of CNV in the first and second eye was 4.5 years. The median age at which vision fell to 20/200 or below was 48 years (first eye) and 54 years (second eye). Argon laser therapy and PDT are not effective in treating CNV of patients with this dystrophy. Antiangiogenic agents may be more effective in this condition. CONCLUSIONS: The main cause of blindness resulting from this dystrophy is CNV. Antiangiogenic agents may be useful in preventing visual loss as a result of this condition.     

Avastin和地塞米松在大鼠角膜新生血管中的作用

目的探讨眼表应用avastin、地塞米松及联合用药对SD大鼠角膜新生血管（CNV）的作用及机制。方法建立碱烧伤诱导大鼠CNV模型,分为4组：地塞米松组给予质量分数0.1%地塞米松局部点眼;avastin组给予5.0g/Lavastin;联合组给予5.0g/Lavastin＋0.1%地塞米松;对照组给予生理盐水。采用裂隙灯观察、免疫组织化学染色等方法观察各组CNV的面积和血管内皮生长因子（VEGF）的表达。结果第6天时,对照组CNV生长接近高峰,血管粗大、密集,交织成网状;地塞米松组和avastin组CNV较短,血管稀疏、细长;联合组CNV较短,血管较稀疏、细小。实验后3、6、12d,3个组CNV面积比较差异均有统计学意义（F=145.659,P=0.000;F=296.370,P=0.000;F=148.008,P=0.000）,组间多重比较显示avastin组、地塞米松组及联合组CNV面积均小于对照组,差异均有统计学意义（P〈0.01）。Avastin组与地塞米松组间差异无统计学意义（P〉0.05）。第7天时,组织病理学检测显示对照组角膜可见大量炎性细胞浸润,基质层大量CNV,胶原纤维排列紊乱;地塞米松组、avastin组角膜基质排列趋于整齐,CNV明显减少,腔小且分布稀疏,未见大量炎性细胞浸润;联合组基质层胶原纤维排列规则,CNV显著减少,炎性细胞浸润较少。免疫组织化学检测提示对照组角膜全层VEGF表达明显增强,其表达部位主要分布在CNV区域和上皮全层。地塞米松组和avastin组CNV密度减低,角膜基质层CNV区域的VEGF表达减少;联合组CNV密度明显减低,VEGF表达微弱。结论 Avastin和地塞米松均能抑制CNV,二者联合用药具有协同作用,可降低CNV和炎性细胞浸润。     

典型性脉络膜新生血管的眼底血管造影对比分析

目的 观察典型性脉络膜新生血管（CNV）的荧光素眼底血管造影（FFA）与吲哚青绿血管造影（ICGA）图像特征的异同。 方法 回顾分析34例（36只眼）典型性CNV患者的FFA和ICGA检查资料，并将FFA与ICGA结果进行对比分析。 结果 FFA显示典型性CNV的早期形态，在15只AMD患眼中有3只眼呈绒团状或车辐状轮廓，占20％；7只病理性近视患眼中有5只眼呈绒团状，占71.4％；14只中心性渗出性脉络膜视网膜病变中有9只眼呈绒团状，占64.3％。36只典型性CNV患眼，ICGA显示清楚的CNV20只眼，占55.6％；ICGA显示欠清楚的CNV15只眼，占41.6％；ICGA未能发现CNV的1只眼，占2.8％；ICGA可显示FFA不能显示的滋养血管6只眼，占16.7％。 结论 典型性CNV的FFA早期形态，AMD中多呈不规则形，而病理性近视和中心性渗出性脉络膜视网膜病变以绒团状居多。ICGA显示典型性CNV的轮廓边界不如FFA清楚，但可发现FFA显示不出的滋养血管。 (中华眼底病杂志, 2006, 22: 217-219)