PDGF抗体和VEGF抗体预防增生性玻璃体视网膜病变

目的评价血小板源性生长因子（PDGF）抗体和血管内皮生长因子（VEGF）抗体对实验性增生性玻璃体视网膜病变（PVR）的预防作用。方法将兔制成PVR模型，将一定浓度的PDGF抗体、VEGF抗体及BSS液分别在当时及第7d注入兔眼的玻璃体腔，每日观察兔眼情况，处死兔子做眼病理切片及免疫组织化学染色。结果间接检眼镜观察可见对照组与实验组均出现视网膜脱离。玻璃体腔内注药后第21d、28dPVR分级实验组与对照组差异有统计学意义（P〈0．05），在制作动物模型时直接注入和第7d时注入差异无统计学意义（P〉0．05）。病理检查所见与间接检眼镜所见相符。免疫组织化学染色计算阳性细胞百分率，亦得出相同结果。结论玻璃体腔内注入PDGF抗体、VEGF抗体均可预防PVR的进展，注药时间对于PVR的发展无明显影响。     

增殖性玻璃体视网膜病变玻璃体血管内皮生长因子的表达

我们以裂孔源性视网膜脱离的增殖性玻璃体视网膜病变 (ｐｒｏｌｉｆｅｒａｔｉｖｅｖｉｔｒｅｏｒｅｔｉｎｏｐａｔｈｙ ,ＰＶＲ)、眼外伤ＰＶＲ为研究对象 ,对其玻璃体血管内皮生长因子 (ｖａｓｃｕｌａｒｅｎｄｏｔｈｅｌｉａｌｇｒｏｗｔｈｆａｃｔｏｒ ,ＶＥＧＦ)进行定量测定 ,研究ＶＥＧＦ在ＰＶＲ中的表达情况 ,分析ＶＥＧＦ在ＰＶＲ中的作用。一、研究对象1 患者组 :选择孔源性视网膜脱离、眼外伤合并ＰＶＲ并行玻璃体切除术治疗的患者 37例。其中孔源性视网膜脱离ＰＶＲ 2 2例 ,男 16例 ,女 6例 ;年龄 2 1～ 5 2岁 ,平均 (36 14±…     

玻璃体注射抗VEGF药物对全身VEGF浓度的影响

脉络膜视网膜疾病已经成为影响人类视力的严重问题,血管内皮生长因子(vascular endothelial growth factor, VEGF)的异常表达导致眼底血管通透性增加和新生血管的形成。玻璃体抗VEGF药物注射可快速抑制眼内VEGF水平,有效控制疾病发展,目前抗VEGF治疗已成为眼科广泛应用的治疗手段。然而,研究表明玻璃体内抗VEGF药物进入循环系统后降低血浆VEGF浓度,药物无意义的脱靶效应可能导致全身不良反应。对于高龄患者、患有严重合并症患者、哺乳期妇女、早产儿等特殊人群,应关注多次注射后的全身VEGF抑制。本文通过探讨抗VEGF治疗的药物代谢动力学、全身不良反应、对侧眼效应、对母乳和早产儿的影响,对玻璃体注射抗VEGF药物的全身影响进行综述,以期对临床抗VEGF治疗提供可参考的信息。     

增殖性玻璃体视网膜病变玻璃体血管内皮生长因子表达的研究

目的　研究血管内皮生长因子 (VEGF)在增殖性玻璃体视网膜病变 (PVR)玻璃体中的表达 ,分析VEGF在 PVR中的作用。方法　增殖性玻璃体视网膜病变 37例 ,其中视网膜脱离 PVR2 2例 2 2眼 ,外伤性 PVR15例。以 12例猝死无眼疾的成年人作为正常对照。检测病例组、对照组玻璃体 VEGF水平。VEGF的测定采用对抗夹心法 (EL ISA)。结果　 37例增殖性玻璃体视网膜病变玻璃体 VEGF平均 2 2 0 .5 2± 10 1.97pg/ m l,其中 2 2例网脱PVR玻璃体 VEGF2 38.90± 6 1.2 4pg/ ml,外伤性 PVR玻璃体 VEGF193.5 8± 5 8.17pg/ ml。正常对照组玻璃体VEGF89.90± 36 .36 pg/ ml。PVR玻璃体 VEGF水平明显高于正常对照组 (P <0 .0 5 )。VEGF在 PVRA级、B级水平较高 ,且随 PVR程度增加而降低。有危险因素 PVR,VEGF水平高于无危险因素 PVR(P <0 .0 5 )。结论　作为细胞间的传导信号 ,VEGF参与 PVR的发生发展。VEGF在 PVR中呈上调性表达。VEGF不仅在缺血性眼部疾病中呈高表达 ,而且在某些非缺血性眼部疾病中表达升高。 VEGF主要在 PVR早期发挥作用 ,PVR危险因素可以刺激玻璃体 VEGF上行性表达。     

增生型糖尿病视网膜病变患者玻璃体血管内皮生长因子及其受体浓度检测

增生型糖尿病视网膜病变(PDR)是影响糖尿病患者视功能的主要原因,其主要病理改变之一是血管生成调节因子间作用失衡导致的新生血管形成[1].研究发现,血管内皮生长因子(VEGF)及其受体在视网膜新生血管的形成中扮演了重要角色[2].其中可溶性VEGF受体-1(sFlt-1)和VEGF受体-2(KDR)是VEGF的主要受体,其在新生血管中的作用多见于肿瘤等疾病的研究,而在玻璃体、视网膜中的含量、分布,尤其是在PDR中研究报道较少[3].我们对一组PDR患者玻璃体中VEGF及其受体的含量进行检测分析,以探讨其在PDR中的可能作用.现将结果报道如下.     

PDR患者玻璃体手术前后房水中VEGF水平的变化

目的：检测增殖性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)患者玻璃体手术前后房水中血管内皮生长因子(vascular endothelial growth factor, VEGF)的浓度变化,研究VEGF在PDR发病机制中的作用。

方法：收集30例PDR患者玻璃体手术前后的房水标本,以30例无糖尿病的白内障患者作为正常对照组,用酶联免疫吸附分析(enzyme-linked immunosorbent assay, ELISA)方法检测VEGF的浓度。

结果：PDR患者与正常对照组相比,房水中VEGF浓度显著升高,有统计学差异(P<0.05)。PDR患者玻璃体视网膜手术后与手术前相比,房水中VEGF浓度显著降低,有统计学差异(P<0.05)。

结论：VEGF积极参与了PDR的发生发展,并与PDR后期新生血管形成有着密切的关系。     

糖尿病视网膜病变患者血浆VEGF和CAMS水平的变化及其临床意义

目的探讨糖尿病视网膜病变患者血浆血管内皮细胞生长因子（vascular endothelial growth factor，VEGF）和细胞黏附分子（cellular adhesion molecules，CAMS）水平的变化及其临床意义。方法采用ELISA法检测58例糖尿病视网膜痛变（diabetic retinopathy，DR）患者血浆VEGF、可溶性细胞间黏附分子-1（soluble intercellular adhesion molecule，sICAM—1）和可溶性血管细胞间黏附分子-1（soluble vascular cellular adhesion molecule，sVCAM-1）的变化，并与非糖尿痛视网膜病变（non—diabetic retinopathy，NDR）患者进行比较。结果糖尿病患者血浆VEGF和sICAM—1、sVCAM—1明显高于对照组，差异有显著性（t’=28．581，20．765，t=19．667，P〈0．001）；DR患者血浆VEGF和sICAM—1、sVCAM—1明显高于NDR患者。差异有显著性（t=11．358～16．025，P〈0．001）；PDR患者VEGF和sICAM-1、sVCAM-1明显高于NPDR患者，差异有显著性（t=5．941～14．547，P〈0．001）。NPDR和PDR患者血浆VEGF与siCAM—1、sVCAM—1呈明显的正相关（r=0.617～0．720。P〈0．01）。结论血浆VEGF和sICAM-1、sVCAM—1水平变化参与了DR的发生与发展，且与病变程度有关。     

放射性视网膜病变患者房水中VEGF的浓度及其临床意义

目的 研究放射性视网膜病变(Radiation Retinopathy)患者房水中血管内皮生长因子(Vascular Endothelial Growth Factor.VEGF)的浓度,明确其对发病的意义.方法 选择2007年3月至2009年3月就诊的放射性视网膜病变患者4例8只眼,增殖性糖尿病性视网膜病变(Proliferative Diabetic Retinopathv,PDR)9名患者10只眼,在行玻璃体腔注入Bevcizumab(1.5mg)治疗前分别抽取100μl前房水;年龄相关性白内障患者10例10只眼,在超声乳化白内障吸除术前,分别抽取lOOμl前房水,所有房水样本均用酶联免疫吸附试验(Enzyme-Linked Immunosorbent Assay,ELISA)检测VEGF浓度.用Kruskal-Wallis H检验对三组患者术前房水中VEGF浓度进行分析,用Mann-Whitney U分别比较三组之间的差异,以P<0.05为差异有统计学意义.结果 放射性视网膜病变与PDR患者房水中VEGF浓度无显著性差异,二者均显著高于白内障患者房水中VEGF水平.结论 放射性视网膜病变患者房水中VEGF浓度显著升高,VEGF可能是引起放射性视网膜病变的重要因素.     

放射性视网膜病变患者房水中VEGF的浓度及其临床意义

目的 研究放射性视网膜病变(Radiation Retinopathy)患者房水中血管内皮生长因子(Vascular Endothelial Growth Factor.VEGF)的浓度,明确其对发病的意义.方法 选择2007年3月至2009年3月就诊的放射性视网膜病变患者4例8只眼,增殖性糖尿病性视网膜病变(Proliferative Diabetic Retinopathv,PDR)9名患者10只眼,在行玻璃体腔注入Bevcizumab(1.5mg)治疗前分别抽取100μl前房水;年龄相关性白内障患者10例10只眼,在超声乳化白内障吸除术前,分别抽取lOOμl前房水,所有房水样本均用酶联免疫吸附试验(Enzyme-Linked Immunosorbent Assay,ELISA)检测VEGF浓度.用Kruskal-Wallis H检验对三组患者术前房水中VEGF浓度进行分析,用Mann-Whitney U分别比较三组之间的差异,以P<0.05为差异有统计学意义.结果 放射性视网膜病变与PDR患者房水中VEGF浓度无显著性差异,二者均显著高于白内障患者房水中VEGF水平.结论 放射性视网膜病变患者房水中VEGF浓度显著升高,VEGF可能是引起放射性视网膜病变的重要因素.     

Nitric oxide and cyclic guanosine monophosphate signaling in the eye

This brief review describes the components and pathways utilized in nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) signaling. Since the discovery of the effects of NO and cGMP on smooth muscle relaxation about 30 years ago, the field has expanded in many directions such that many, but not all, biochemical and biological effects seem to be regulated by these unique signaling molecules. While many of the effects of NO are due to activation of soluble guanylyl cyclase (sGC) that can be considered the receptor for NO, cGMP, in turn, can activate a cGMP-dependent protein kinase (PKG) to phosphorylate an array of proteins. Some of the effects of cGMP can be independent of PKG and are due to effects on ion channels or cyclic nucleotide phosphodiesterases. Also, some of the effects of NO can be independent of sGC activation. The isoenzymes and macromolecules that participate in these signaling pathways can serve as molecular targets to identify compounds that increase or decrease their activation and thus serve as chemical leads for discovering novel drugs for a variety of diseases. Some examples are given. However, with about 90,000 publications in the field since our first reports in 1977, this brief review can only give the readers a sample of the excitement and opportunities we have found in this cell signaling system.     

一氧化氮与视网膜缺血-再灌注损伤

一氧化氮（NO）在视网膜缺血-再灌注损伤中占重要地位。视网膜缺血-再灌注时,一氧化氮合成酶（NOS）被多种炎性介质和细胞因子激活,使NO大量生成。NO是一种活性很强的自由基,具有广泛的生物学活性。在缺血-再灌注早期,少量NO可降低缺血缺氧对视网膜的损伤程度;晚期过多的NO可通过多种途径对视网膜造成损害。就目前有关NO在视网膜缺血-再灌注损伤中的研究进展进行综述。     

Nitric oxide and octreotide in retinal ischemia-reperfusion injury

This experimental study was performed to investigate the role of ischemia–reperfusion injury on retinal nitric oxide activity and to determine whether octreotide, the synthetic analogue of natural somatostatin, modifies the nitric oxide activity during retinal ischemia–reperfusion in a quinea pig model. Three groups of seven pigmented male quinea pigs were formed; Control, Ischemia and the Ischemia/Octreotide groups. 90 minutes of pressure-induced retinal ischemia and 24 h of reperfusion were established in the ischemia and ischemia/octreotide groups. Saline for the ischemia group and 50 g/kg of octreotide for the ischemia/octreotide group were administered intraperitoneally five times with 6-h intervals. At the end of the reperfusion period both eyes of the animals of the three groups were enucleated. One eye of each animal was randomly selected for biochemical assay and the other for histopathological analysis. Retinal nitrate levels were measured and histopathological changes were evaluated in the groups. The mean retinal nitrate levels of the control, ischemia and ischemia/octreotide groups were 157.6±25.2, 106.4±20.1 and 96.4±17.7 mol/l, respectively. Nitrate levels decreased significantly both in the ischemia (p<0.01) and ischemia/octreotide (p<0.01) groups versus control. In the ischemia group, retinal histopathological changes, which were different from the control group, were prominent edema, polymorphonucleated leukocytes infiltration and vacuolated spaces in the inner retina. No significant change was observed in the histopathological specimens of the ischemia/octreotide group. Significant increase in the thickness of the inner plexiform layer of the retina of the ischemia group was observed versus the control and ischemia/octreotide groups (p<0.01 and p<0.01, respectively).The thickness of the inner plexiform layer of the retina of the ischemia/octreotide group did not change versus the control group. It was concluded that nitric oxide activity decreased during retinal ischemia–reperfusion and, although octreotide prevented the histopathological damage, it could not ameliorate the nitric oxide activity of the retina.This study was presented in part at the 23rd Congress of the European Society of Ophthalmology.     

VEGF家族及其受体与糖尿病视网膜病变发病的关系

视网膜新生血管形成和黄斑水肿是糖尿病视网膜病变(diabetic retinopathy,DR)的主要临床表现,也是DR主要的致盲原因。目前研究表明血管内皮生长因子(vascular endothelial growth factor,VEGF)在糖尿病视网膜微血管并发症的发生中发挥重要作用,因此VEGF成为当今DR治疗干预的一个研究热点。本文就VEGF家族及其受体在DR中的表达与DR病变发病的关系研究进展进行综述。     

青光眼患者血清及房水一氧化氮浓度的测定

目的 测定青光眼患者血清及房水一氧化氮(NO)浓度并探讨其在青光眼发病中的作用。方法 实验患者分为青光眼组和白内障组,应用硝酸还原酶法分别测定两组患者血清及房水NO浓度。结果 两组患者血清NO浓度无显著性差异,青光眼组内各类型之间血清NO浓度亦无显著性差异。原发性开角型青光眼患者房水NO浓度较对照组及其他类型青光眼显著降低,闭角型青光眼患者房水NO浓度较对照组显著升高(P<0.01)。 结论 眼压升高可引起房水NO浓度升高,过多的NO可损伤小梁网及邻近的葡萄膜及视网膜组织。开角型青光眼患者由于房角原生型一氧化氮合成酶的减少引起房水NO浓度的降低,此可能为眼压升高的原因之一。     

培养的牛视网膜毛细血管周细胞产生一氧化氮的影响

目的 观察糖基化终产物(ACE)、脂多糖(LPS)及低氧对培养的牛视网膜毛细血管周细胞(BRPs)内一氧化氮(NO)产生的影响。方法 培养的BRPs分别与不同质量浓度的AGE(8、32、125、500μg/ml)共同培养4d;LPS(10、20、40μg/ml)共同培养24h;低氧(5％O_2、5％CO_2、90％N_2)条件下培养12、24、48h。培养结束后,分别收集培养液,离心取上清液,用硝酸还原酶法检测其NO的浓度。结果 基础状态下,BRPs上清液中NO浓度为(37.25±4.37)μmol/L。低剂量的AGE(8μg/ml)与BRPs共同培养4d后,其上清液中NO的浓度为(68.37±9.92)μmol/L,是基础状态下BRPs上清液中NO浓度的1.8倍,随着AGE质量浓度的增加,BRPs上清液中NO的浓度迅速减少(r=0.835,P<0.01)。LPS及低氧能使BRPs产生NO明显增加(t=2.88,P<0.05及t=4.56,P<0.01),随着LPS质量浓度的增加和低氧时间的延长,BRPs上清液中NO的浓度也迅速上升(r=0.951,P<0.01和r=0.955,P<0.01)。结论 AGE、LPS和低氧能调节BRPs中NO的产生,NO与视网膜微循环血流动力学的调节有关。     

VEGF localisation in diabetic retinopathy

AIM—To determine the staining pattern of vascular endothelial growth factor (VEGF) at different stages of diabetic retinopathy (including post-laser photocoagulation) and to compare staining in excised fibrovascular and fibrocellular (non-diabetic) preretinal membranes.
METHODS—Immunohistochemical localisation of VEGF, using antibodies raised against VEGF₁₆₅ and VEGF_121,165,189, was carried out on specimens of normal human retina (n=15), diabetic retinas ((a) with no overt retinopathy (n=19), (b) with intraretinal vascular abnormalities but no proliferative retinopathy (n=6), (c) with active proliferative retinopathy (n=6), (d) with no residual proliferative retinopathy after photocoagulation therapy (n=15)), excised diabetic fibrovascular membranes (n=19), and non-diabetic fibrocellular membranes (n=7). The degree and pattern of immunostaining was recorded.
RESULTS—In general, VEGF was absent from the majority of normal retinas. VEGF staining was apparent in most diabetic tissues but the staining pattern was dependent on both the specificity of the antibody used and the category of tissue. Staining with the VEGF₁₆₅ antibody was generally confined to endothelial cells and perivascular regions while the VEGF_121,165,189 antibody was also associated with extravascular components of the inner retina. Intensity of immunostaining of diabetic eyes was dependent on the severity of retinopathy being least in diabetics with no overt retinopathy and greatest in retinas with proliferative retinopathy. Interestingly, the intensity of immunostaining in diabetic retinas which had undergone laser surgery for proliferative retinopathy was reduced to basal levels. Moderate to intense immunostaining was observed in all fibrovascular and fibrocellular membranes examined.
CONCLUSIONS—This study supports a circumstantial role for VEGF in the pathogenesis of both the preclinical and proliferative stages of diabetic retinopathy.

Keywords: vascular endothelial growth factor; VEGF; diabetes; diabetic retinopathy     

氧诱导小鼠视网膜组织VEGF和iNOS的早期表达及意义

目的明确血管内皮生长因子（VEGF）和诱导型一氧化氮合酶（iNOS）在氧诱导小鼠视网膜组织中早期的表达特征,并探讨上述促血管生成因子的表达在缺氧状态下视网膜新生血管生成中的意义。方法新生C57BL/6J小鼠暴露于高氧环境5d后转置于相对低氧环境,以建立视网膜新生血管小鼠模型,分别于暴露低氧环境0、2、6、24h后摘除眼球,应用RT-PCR及免疫组织化学技术检测全视网膜组织中VEGF及iNOS的表达情况。结果在低氧环境下,VEGF的表达水平呈现较明显的时间依赖性特征,与0h时间点相比,缺氧2hVEGFmRNA表达升高,6h尤为明显,24h下降。iNOSmRNA表达亦呈相似的特征,其表达高峰出现在缺氧2h,6h起即呈逐渐下降趋势。VEGF主要定位于视网膜节细胞层（RGCL）及内网层（IPL）的细胞浆,而iNOS蛋白表达于GCL的细胞浆;上述蛋白表达亦呈现与基因转录水平相一致的时间依赖性。结论暴露于缺氧环境下24h内视网膜VEGF和iNOS表达均上调,且随暴露时间呈动态变化,提示视网膜缺氧性病变早期即出现促血管生成因子的表达变化。