药物治疗视网膜新生血管的研究进展

视网膜新生血管与许多眼部疾病有关,是引起视力障碍的重要原因之一,目前临床上尚无特殊有效的药物治疗方法。我们对视网膜新生血管发生机制、药物治疗措施方面的现状及进展作一综述。     

药物治疗视网膜下新生血管的研究进展

视网膜下新生血管(subretinal neovascularization，SRNV)也称为脉络膜新生血管(choroidal neovascularization，CNV)，是由多种病因所致的脉络膜新生血管穿越Bruch膜并在视网膜色素上皮下和(或)视网膜神经感觉层下增殖形成的纤维血管组织，为导致年龄相关性黄斑变性(age-related macular     

视网膜新生血管的治疗研究进展

视网膜新生血管的发生是众多促血管生成因子间协同作用的结果.病理状态下以基质金属蛋白酶、促红细胞生成素、整合素为代表的促血管生成因子,可通过不同的作用途径,促进视网膜新生血管的发生.有研究者将促视网膜新生血管形成因子作为"靶点"进行靶向治疗研究,可有效地抑制视网膜新生血管的发生.为进一步了解其靶向治疗的机制和效果,有必要就视网膜新生血管形成中的靶分子和靶向治疗研究进展予以阐述,以期为视网膜新生血管的临床治疗提供理论依据.     

视网膜新生血管生物药物治疗研究进展

眼内新生血管的发生是许多眼病的病理基础和重要临床表现,而血管内皮生长因子(VEGF)是刺激不正常的血管生长以及造成血管壁渗漏的主因,因此抗VEGF靶分子治疗成为当今的研究热点.本文综述了近年来视网膜新生血管生物药物治疗新进展,包括VEGF反义寡聚脱氧核苷酸、VEGF抗体、RNA干扰类药物等.这些方法均显示出令人振奋的效果,但仍需要经过长期、系统的临床试验检验其安全性、有效性.     

抗眼底新生血管药物的研究进展

视网膜和脉络膜新生血管可引发玻璃体出血、视网膜下出血、牵引性视网膜脱离等,从而危害患眼视力。这类病变常见于老年性黄斑变性(age related macular degeneration,AMD)、糖尿病视网膜病变(diabetic retinopathy,DR)、视网膜静脉阻塞(retinal vein occlusions,RVO)、早产儿视网膜病变(retinopathy of prematurity,ROP)等眼底病。当前,药物治疗新生血管(neovscularization,NV)主要是针对NV生成的不同阶段抑制其生长。本文综述了目前已用于临床及正在进行临床试验的治疗眼底新生血管的药物。     

视网膜与新生血管抑制因子

抑制新生血管生长是视网膜新生血管性疾病的治疗关键。促生长因子和抑制因子共同调控血管的形成，二的平衡控制新生血管的生成。新生血管抑制因子的治疗已成为有前景的新生血管治疗方法。本就与视网膜新生血管研究有关的新生血管抑制因子研究进展进行综述。     

MicroRNA调节视网膜新生血管研究进展

视网膜新生血管是导致失明的主要原因之一,近年来研究表明,血管新生与多种生长因子有着密切的关系,microRNA(miRNA)可能调控这些生长因子的表达.一些miRNA被证明与视网膜新生血管关系密切,例如miR-31、miR-150、miR-184、miR-200 b、miR-126等,它们通过影响相应靶基因的表调控血管新生.miRNA类似物或拮抗物调控血管新生相关因子的已逐渐成为新生血管疾病的治疗新策略,本文对此进行相关综述.     

角膜新生血管的药物治疗进展

角膜在病理因素的作用下产生新生血管。角膜新生血管不但严重影响视力,而且导致角膜移植手术的失败。近年来,国内外对角膜新生血管的治疗取得迅猛发展,但角膜新生血管依然是目前最常见的致盲原因之一。本文综述了近年来角膜新生血管的药物治疗进展。     

视网膜新生血管动物模型的制备

目的制备视网膜新生血管动物模型,为今后的视网膜新生血管相关疾病的研究提供稳定的模型.方法以出生7d的C57BL/6J小鼠56只,雌雄兼有,随机将28只放入75%±2%高氧环境,控制室温23℃±2℃,日光照明,5d后返回空气环境;另一组28只置于23℃±2℃空气环境中饲养作为对照.随机于出生后12、14、17、21、22、25d取高氧组和空气组小鼠行视网膜铺片、血管内皮生长因子(vascular endothelial growth factor,VEGF)免疫组化染色,观察VEGF的表达情况,并对出生后17d小鼠的视网膜铺片、石蜡切片HE染色、VEGF免疫组化染色.结果高氧诱导组出生后17d视网膜无血管区面积,穿过视网膜内界膜细胞核计数明显高于空气组.血管内皮细胞VEGF的表达从出生后14d开始有阳性表达,阳性表达逐渐增强,出生后17d达到高峰,之后逐渐下降,持续至出生后21d.结论该模型为一种合适的视网膜新生血管动物模型.     

ILK治疗视网膜新生血管研究热点

整合素连接激酶（integrin-linked kinase,ILK）是一种最近发现的能够与整合素β1、β3亚基胞浆域结合的丝氨酸/苏氨酸蛋白激酶,它包含三个独特的结构域：N末端4个锚蛋白（ankyrin,ANK）重复序列,C末端激酶结构域,两者之间是磷脂酰肌醇结合结构域（phosphinositide binding motif）,简称PH结构域。ILK是PI-3K信号传导通路的重要成员,PI-3K产物PIP3与ILK的PH结构域结合后使之活化,进一步可以通过磷酸化下游底物PKB/AKT、GSK-3促进VEGF的表达;另一方面VEGF与相应的受体结合后也可以激活ILK,活化的ILK进一步通过调节细胞增殖,侵袭和凋亡过程参与调控VEGF诱导的新生血管形成。因此抑制ILK功能可能产生的这种双重作用效果——抑制VEGF的表达、抑制VEGF诱导的血管网形成——表明ILK很可能成为治疗视网膜新生血管的新思路。     

Bevacizumab联合视网膜光凝治疗虹膜和视网膜新生血管

目的:观察Bevacizumab玻璃体腔注射联合视网膜光凝治疗虹膜和视网膜新生血管的疗效和安全性。方法:回顾分析虹膜和视网膜新生血管患者13例13眼玻璃体腔注射Bevacizumab联合视网膜光凝治疗的临床随访资料。13眼中视网膜新生血管9眼(其中继发于视网膜分支静脉阻塞的2眼,增生型糖尿病视网膜病变的6眼,Eales病的1眼),虹膜新生血管4眼(均继发于视网膜中央静脉阻塞)。13眼全部行玻璃体腔注射1.25mg/0.05mL的Bevacizumab,术前或术后分次补充完成视网膜光凝。随诊3～18mo,随访期间发现新生血管复发者,再行同样方法的注射和光凝治疗。观察治疗前后最佳矫正视力、眼压、眼底荧光血管造影。结果:经治疗后,13眼中8眼(61.5%)视力提高,4眼(30.8%)视力保持不变,1眼(7.7%)视力下降;6例合并玻璃体积血,术后均明显吸收;13眼视网膜及虹膜新生血管均消退,随诊期间复发2眼,行第二次注射和光凝治疗后新生血管无复发。虹膜新生血管(新生血管性青光眼)4眼中2眼治疗后眼压下降,随访期间均控制正常,另2眼联合青光眼阀植入后眼压控制正常。随诊期中,其余9眼眼压无升高。1例患者注药后结膜下出血,其余患者未出现其他并发症。结论:Bevacizumab玻璃体腔注射联合视网膜光凝治疗虹膜和视网膜新生血管在短期内能促进玻璃体积血吸收和新生血管萎缩,副作用少;但尚需进一步大样本、多中心的临床随机对照研究。     

孔源性视网膜脱离后视网膜新生血管的实验研究

目的：观察孔源性视网膜脱离（RRD）后新生血管的形成及形态学改变。方法：采用玻璃体手术制备25只眼RRD模型,排除失败的5只眼后,将20只眼分为5组,每组4只兔（眼）。分别在RRD第1,4,7,14和28天,观察新生血管的形态学改变。结果：RRD1和4天,未见新生血管。7天可见视备用新生血管。14天眼底荧光造影可见新生血管末梢渗漏。但主干枝无渗漏。14-28天,以视盘为中心的新生血管范围逐渐扩大,部分新生血管已发育成熟。虹膜无新生血管形成。结论：随着RRD时间的延长,视网膜新生血管范围逐渐扩大,并逐渐发育成熟,新生血管是一种视网膜缺氧的代偿性反应。     

Peripheral retinal neovascularization in diabetes mellitus

The cases of seven patients with diabetes mellitus and peripheral proliferative retinopathy (retinal neovascularization at or anterior to the equator) were studied. Associated abnormalities found included systemic arterial hypertension in five, a positive fluorescent treponemal antibody titer in four, and benign monoclonal gammopathy, intravenous drug abuse and hemoglobin AS each in one patient. The presence of additional systemic diseases should be suspected in diabetic patients with predominantly peripheral proliferative retinopathy.     

Unilateral retinal vasculitis,branch retinal artery occlusion and subsequent retinal neovascularization in Crohn's disease

Purpose: To report on a case of Crohn's disease and unilateral retinal vasculitis, branch retinal artery occlusion and subsequent retinal neovascularization. Methods: We examined a 38-year-old woman with severe left visual loss and biopsy-proven Crohn's disease diagnosed four years prior to the ocular involvement. A Heidelberg scanning laser ophthalmoscope was used for fundus fluorescein angiography and indocyanine green angiography. Retinal neovascularization was detected during the follow-up. Results: Successful regression of retinal neovascularization was achieved after argon green laserpanretinal photocoagulation in addition to oral steroid and salazopyrine. Conclusion: Retinal vascular involvement is a rare ocular feature of Crohn's disease and may result in retinal neovascularization that may necessitate prompt laser photocoagulation.     

小鼠视网膜新生血管模型的建立及特征

目的:建立可靠稳定的视网膜新生血管动物模型,为今后探究视网膜新生血管疾病的发生机制和治疗方法奠定模型基础。方法:将24只新生C57BL/6J小鼠随机分为正常组和模型组,每组各12只。将模型组小鼠于生后第7d置于750mL/L氧浓度环境,生后第12d返回正常空气中;正常组小鼠始终置于正常空气环境喂养。至小鼠生后第17d进行心脏荧光素灌注造影视网膜铺片以及眼球连续切片苏木精-伊红(H-E)染色,观测视网膜新生血管生成情况。结果:模型组小鼠心脏荧光素灌注造影结果显示视网膜中央区域呈无灌注缺血,另外视网膜血管有迂曲扩张、荧光渗漏等异常表现。眼球连续切片发现模型组小鼠突出视网膜内界膜的血管内皮细胞核数为48.65±6.24个/片/眼,而正常组小鼠平均为0.38±0.21个/片/眼,两组比较差异有显著统计学意义(P<0.01)。结论:氧诱导的视网膜缺血模型可成功诱导小鼠产生视网膜新生血管,可作为探究视网膜新生血管疾病发生机制和治疗方法的可靠动物模型。     

Inhibitory effect of captopril on retinal neovascularization in mice

AIM: To study the inhibitory effect of captopril on retinal neovascularization (RNV). METHODS: Sixty seven-day-old mice were randomly divided into treated group and control group with thirty mice in each group. These mice were exposed to 750 ± 50mL/L oxygen for 5 days and then to room air. The treated group had been injected captopril (2.7mL/kg), while control group had been injected 9g/L sodium chloride (2.7mL/kg) by intravitreal for 5 days. The mice were sacrificed at the 17th day after birth and the eyes were enucleated. Adenosine diphosphate-ase (ADPase) stained retina flat-mounts was performed to assess the retinal vascular profiles, Hematoxylin Eosin (HE) staining method was applied to count the number of new vascular cell nuclei and the expression of matrix metalloproteinase-2 (MMP-2) and pigment epithelium derived factor (PEDF) was detected by immunohistochemical method. · RESULTS: Comparing with control group, regular distributions, good branch and reduced density of RNV were observed in the treated group. The number of nucleus of new vessels vascular endothelial cells breaking through the internal limiting membrane was less in the treated group than in the control group ( <0.05). Stain of retinal MMP-2 was weaker in the treated group than in the control group and stain of retinal PEDF was stronger in the treated group than in the control group. CONCLUSION: Intravitreal injection of captopril (2.7mL/kg) may block the RNV in the oxygen-induced mouse model and the method may provide an effective method for preventing RNV.     

抗代谢药物8-氯腺苷抑制兔实验性视网膜新生血管的研究

目的探讨抗代谢药物8-氯腺苷(8-Cl-A)眼局部应用对兔实验性视网膜新生血管的抑制作用。设计实验研究。研究对象纯种青紫兰家兔40只。方法采用视网膜静脉直接光凝法建立兔视网膜静脉阻塞(RVO)模型。分别设立对照组及8-Cl-A给药组,每组各20只(20眼)。于造模后次日治疗组每日球后注射8-Cl-A 9mg(计10日),对照组注射等体积生理盐水,采用荧光素眼底血管造影观察注射后2周内2组兔视网膜新生血管的发生率,并进行统计学分析。主要指标视网膜新生血管发生率及程度。结果RVO对照组20眼中,17跟发生视网膜新生血管:8-Cl-A治疗组20眼中3眼发生光凝点远端的视网膜新生血管(P= 0.000),且发生的程度及范围小于对照组,同时未见视网膜静脉侧支循环的建立。结论8-Cl-A可有效抑制兔实验性视网膜新生血管的发生。在视网膜血管增生性病变治疗中可能具有潜在的临床应用价值。     

AE-941抑制鼠视网膜新生血管的实验研究

目的探讨AE-941（CARTCELL卡特消）对视网膜新生血管形成的抑制作用。方法将鼠龄为7天的Wistar幼鼠置于75％浓度的氧环境中连续生活5天，建立高氧诱导的血管增生性视网膜病变幼鼠模型。随机分为正常对照、给氧对照组及治疗组（幼鼠玻璃体腔内注射AE-9410．25mg，0．5μl，1mg／ml，对侧眼注射相同体积的生理盐水作为对照）。采用ADP酶组织化学法行视网膜铺片，了解视网膜血管改变；用组织切片观察并计数突破视网膜内界膜的血管内皮细胞核数目，观察卡特消对视网膜新生血管形成的抑制情况。结果给氧对照组（鼠龄17天）可见视网膜血管分布紊乱、密度增高，大量的视网膜新生血管，组织切片上可见较多突破视网膜内界膜的血管内皮细胞核。治疗组视网膜血管分布规则、密度减少，突破内界膜的内皮细胞细胞核数目明显减少，两组差异有显著统计学意义（P〈0．001）。结论AE-941可以抑制视网膜新生血管形成，有望成为防治血管增生性视网膜病变的一种有效的方法。     

Ocular neovascularization with retinal vascular occlusion-III. Incidence of ocular neovascularization with retinal vein occlusion

A prospective natural history study was conducted in 721 eyes with various types of retinal vein occlusion (RVO) to determine the incidence of various types of ocular neovascularization (NV) and the factors that influence the development of ocular NV. The material was 360 eyes with central retinal vein occlusion (CRVO), 97 eyes with hemi-CRVO, and 264 eyes with branch retinal vein occlusion (BRVO); these cases were further subdivided into six groups for logical data analysis: nonischemic CRVO (venous stasis retinopathy-VSR, 282 eyes), ischemic CRVO (hemorrhagic retinopathy-HR, 78 eyes), hemi-VSR (66 eyes), hemi-HR (31 eyes), major BRVO (191 eyes) and macular BRVO (73 eyes). Ocular NV attributable to RVO was seen only in HR, hemi-HR, and major BRVO. In HR the anterior segment was the major site of NV, with iris and angle NV and neovascular glaucoma (NVG), while in hemi-HR and major BRVO the retina and optic disc were the major sites of NV. The principal factor influencing the development of ocular NV in RVO seems to be the severity and extent of retinal ischemia, while duration of follow-up since onset also plays an important role in determining the incidence of ocular NV. The findings and subject of ocular NV in RVO are discussed in detail along with a review of the pertinent literature.