血管内皮生长因子和第Ⅷ因子相关抗原在脑出血大鼠脑内的表达

目的　探讨脑出血大鼠血管内皮生长因子 (VEGF)、第Ⅷ因子相关抗原 (FⅧ RAg)表达变化及其意义。方法　采用胶原酶诱导大鼠脑出血模型。应用免疫组织化学方法检测VEGF、第Ⅷ因子相关抗原在血肿周围区脑组织的表达。结果　脑出血 12h～ 7d血肿周围区表达VEGF阳性细胞数量逐渐增多 ,但每个阳性细胞平均吸光度 (A ,曾称为光密度OD)值无显著变化。脑出血 12h时 ,以FⅧ RAg标记的微血管密度和平均A值与对照组比较无显著性差异 ,1d后微血管密度和A值逐渐增高。结论　脑出血后血肿周围组织VEGF的高表达可促进内皮细胞增生 ,新生血管形成     

Müller glial cells inhibit proliferation of retinal endothelial cells via TGF‐β2 and Smad signaling

Neovascularization is a sight‐threatening complication of ischemic proliferative retinopathies. Transforming growth factor (TGF)‐β, a cytokine with multiple functions in the retina, participates in the control of pathological angiogenesis and neovascularization. Retinal glial (Müller) cells produce TGF‐β2 under physiological and post‐ischemic conditions. To characterize glial cell‐derived mediators of angiogenesis regulation in glial‐endothelial interactions in the retina, we co‐cultured primary Müller cells and bovine microvascular retinal endothelial cells (BRECs). Müller cell‐derived TGF‐β2 was bound by the BRECs, which were found to express serine/threonine kinase TGF‐β receptors, and stimulated TGF‐β‐dependent anti‐proliferative signaling pathways. The proliferation of BRECs was attenuated by exogenous TGF‐β2 as well as by the presence of Müller cell culture media. The following intracellular signaling mechanisms were found to be involved in the anti‐angiogenic action of Müller cell‐derived TGF‐β2: (i) binding of TGF‐β2 to BRECs is mediated by the type‐II TGF‐β receptor, leading to (ii) activation and phosphorylation of receptor‐activated Smads; (iii) Müller cell‐derived TGF‐β2 activates Smad2 and Smad3 to (iv) attenuate the phosphorylation state of the MAP kinases, extracellular signal‐regulated kinase (ERK)‐1/‐2. Neutralizing TGF‐β or TGF‐β type‐II receptor or blocking the activation of Smads partially abrogated the effect of Müller cell‐conditioned media on BRECs. Together, our data suggest that Müller cells release TGF‐β2, inhibiting the proliferation of retinal endothelial cells via activation of Smad2/Smad3 and attenuation of ERK signaling. Given the context‐dependent action of TGF‐β2 on angiogenesis, our results may have implications for understanding the pathogenesis of retinal angiopathies, such as diabetic retinopathy, and the anti‐angiogenic role of TGF‐β therein. GLIA 2014;62:1476–1485     

Hyperbaric oxygen preconditioning promotes neovascularization of transplanted skin flaps in rats

To determine whether Hyperbaric oxygen preconditioning (HBO-PC) promotes neovascularization by increasing Stromal cell derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) in transplanted skin flaps of rats. The epigastric pedicle skin flap was established in a rat model. Rats were randomly assigned to the following five groups: 1) sham-operated group (SH); 2) ischemia followed by reperfusion 3 days postoperatively group (IR3d); 3) ischemia followed by reperfusion 5 days postoperatively group (IR5d); 4) hyperbaric oxygen preconditioning and ischemia followed by reperfusion 3 days postoperatively group (HBO-PC3d); and 5) hyperbaric oxygen preconditioning and ischemia followed by reperfusion 5 days postoperatively group(HBO-PC5d). For the groups receiving HBO-PC, animals underwent 1 hour of HBO at 2.0 ATA in 100% O₂ twice per day for 3 days consecutively prior to surgery. After perfusion, Laser Doppler perfusion imaging (LDPI) was performed, and skin flap tissue samples were harvested for histological evaluation and western blot analysis. Perfusion was significantly improved in the HBO-PC groups compared with the IR groups on postoperative 3 and 5. Microvessel density (MVD) was significantly increased by HBO-PC compared with IR groups postoperatively. Western blot analysis revealed that SDF-1 and CXCR4 expression in the HBO-PC groups was significantly increased compared with IR groups. HBO-PC promoted neovascularization via increasing expression levels of SDF-1 and CXCR4 in transplanted skin flaps of rats.     

柚皮素β-环糊精包合物的制备及对模型大鼠脉络膜新生血管形成的抑制作用

目的:制备柚皮素β-环糊精(β-CD)包合物,研究其对模型大鼠脉络膜新生血管(CNV)形成的抑制作用。方法:采用饱和溶液法制备柚皮素β-CD包合物;利用红外光谱、X射线衍射法对包合物进行表征分析,测定柚皮素的含量与水溶解度;通过氪激光复制大鼠CNV模型,15只BN大鼠随机均分为溶媒对照(等容溶媒)组、柚皮素(20 mg/kg)组与柚皮素β-CD包合物(97.4 mg/kg)组,腹腔注射给药,每天1次,连续4周。以脉络膜铺片法测量大鼠CNV面积。结果:柚皮素和β-CD形成了稳定的包合物,柚皮素β-CD包合物中柚皮素质量分数为20.53%,柚皮素在水中的溶解度为单体的11.8倍。与溶媒对照组比较,柚皮素组、柚皮素β-CD包合物组大鼠CNV面积减小,差异有统计学意义(P<0.01或P<0.05);与柚皮素组比较,柚皮素β-CD包合物组大鼠CNV面积减小,差异有统计学意义(P<0.05)。结论:柚皮素和β-CD包合后,水溶性增加;柚皮素β-CD包合物抑制模型大鼠CNV形成的作用优于柚皮素。     

Long‐term efficacy and safety of ranibizumab administered pro re nata in Japanese patients with neovascular age‐related macular degeneration in the EXTEND‐I study

Purpose: To evaluate the long‐term efficacy and safety of ranibizumab administered pro re nata (PRN) in Japanese patients with choroidal neovascularization secondary to age‐related macular degeneration during the extension phase of the EXTEND‐I study. Methods: EXTEND‐I, an open‐label, multicenter, Phase I/II study comprised: a single‐injection (Group A); a multiple‐injection (Groups A and B; the latter consisted of patients who did not participate in the single‐injection phase); and an extension phase. In the extension phase, a PRN regimen of ranibizumab (0.3 or 0.5 mg) guided by monthly best‐corrected visual acuity (BCVA) score and other ophthalmic examinations was employed. The efficacy variables included the mean BCVA change from Month 12 to the last visit in Group B. Safety was assessed in all patients. Results: In the extension phase, efficacy was assessed only in Group B patients. The number of ranibizumab injections per year in the 0.3 and 0.5 mg Group B patients was 4.19 and 4.27, respectively. The mean BCVA change (SD) from Month 12 to the last visit was ?3.6 (14.82) letters for 0.3 mg (n = 28) and ?2.2 (7.92) letters for 0.5 mg groups (n = 33) in Group B. Conjunctival haemorrhage and nasopharyngitis were the most commonly reported adverse events. Of the 13 serious adverse events reported, cerebral infarction (two incidences) was suspected to be study‐drug related. Conclusions: Pro re nata regimen of ranibizumab guided by monthly BCVA and other ophthalmic examinations appears effective in sustaining the BCVA gained with 12 monthly injections while reducing the number of injections during the extension phase. Ranibizumab was well tolerated during the extension phase.     

大鼠角膜碱烧伤行培养角膜上皮移植后VEGF的表达

目的 研究角膜上皮培养移植后角膜新生血管(CNV)形成和血管内皮生长因子(VEGF)的变化特点.方法 对角膜碱烧伤CNV大鼠行培养角膜上皮移植,观察术后CNV程度,RT-PCR和免疫组织化学法检测术后24、48、72、168 h角膜组织VEGF的表达.结果 实验组角膜上皮移植后14 d CNV接近瞳孔区,之后逐渐减退.移植后24 h角膜VEGF mRNA的相对含量为1 20±0.09;48 h为1 91±0.03;72 h为2.34±0.11;168 h为1.83 ±0.14.角膜上皮和基质均表达VEGF蛋白,以上皮层表达为主,并随时间推移表达量增加.结论 培养角膜上皮移植后24 h角膜可表达VEGF,72 h表达量最高.VEGF表达与培养角膜上皮移植后CNV的发生密切相关.     

CD105与脉络膜新生血管

CD105(endoglin)为一种同型二聚体的膜结合性糖蛋白,是转化生长因子-β(transforming growth factor,TGF-β)受体超家族的成员之一。它参与TGF-β受体的信号转导,调节细胞对TGF-β的反应,在新生血管组织及肿瘤组织边缘部分血管起源的内皮细胞中高度表达,是新生血管的标志物之一。脉络膜新生血管(choroidal neovasculariza-tion,CNV)的生成是年龄相关性黄斑变性(age-related macular degeneration,AMD)、眼拟组织胞浆菌病综合征(presumed ocular histoplasmosis syndrome,POHS)和病理性近视黄斑变性等CNV相关疾病的的主要病理特征。近年研究表明,CD105与CNV密切相关,可能成为治疗CNV重要的靶分子之一。     

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。     

Avastin在眼科应用的研究进展

Avastin是第一个被美国FDA批准的通过抑制血管生成发挥抗癌作用的新药,是现行几种抗血管生成制剂之一,可抑制血管内皮生长因子(VEGF)的生成,近年研究表明,该药在治疗眼部新生血管性以及渗出性病变中疗效显著,而且价格便宜,应用前景十分广阔。