新生血管性眼病的治疗进展

随着人口老龄化和生活质量的提高,以年龄相关性黄斑变性及糖尿病性视网膜病变为主的新生血管性眼病正日益成为影响患者生活质量的主要因素。新生血管性眼病以新生血管形成为主要病理表现,病因复杂、机制多样、预后不佳是其主要特征。近年来激光、抗VEGF药物及手术等多种药物和治疗方法的不断涌现与改进,为该类疾病的治疗带来更多更好的疗法。本文就这一系列新生血管性眼病的治疗进展予以综述。     

VEGF对大鼠50%减体积肝脏移植术后肝再生的影响

目的探讨血管内皮生长因子(VEGF)对大鼠减体积肝移植术后肝脏再生的影响。方法建立大鼠50%减体积肝移植模型,分3组,VEGF治疗组、anti-VEGF组、对照组。分别于术后注射鼠重组VEGF、anti-VEGF、生理盐水(NaCl)。在术后不同时相点测定肝细胞核增殖蛋白抗原(PCNA)表达指数,测定血清HGFI、L-6的含量,测定术后肝脏生化指标。结果VEGF组术后肝细胞PCNA表达指数较对照组升高,anti-VEGF组较对照组降低,差异有统计学意义。anti-VEGF组天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)较VEGF组及对照组升高,差异有统计学意义。VEGF组术后血清HGFI、L-6浓度较对照组增高,anti-VEGF组较对照组明显减弱。结论VEGF治疗增强大鼠减体积肝移植术后肝脏再生活性,改善术后肝功能。这可能与VEGF促进肝脏HGFI、L-6分泌有关。     

VEGF对大鼠50%肝脏移植术后血清HGF、IL-6浓度的影响

目的 探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)对大鼠部分肝移植术后血清肝细胞生长因子(hepatocyte growth factor,HGF)、白细胞介素-6(interleukin-6,IL-6)浓度的影响.方法 建立大鼠50%部分肝移植模型.实验动物分3组:VEGF治疗组、anti-VEGF组、对照组.分别于术后注射鼠重组VEGF、 anti-VEGF、生理盐水.在术后不同时相点(0、12、24、72、168 h)测血清中HGF、IL-6 含量及肝脏生化指标.结果 VEGF组血清HGF、IL-6水平较对照组明显增高,anti-VEGF组较对照组明显降低,有显著差异.anti-VEGF 组天冬氨酸转氨酶(aspartate aminotransferase,AST)、丙氨酸转氨酶(alanine aminotransferase,ALT)较VEGF组及对照组明显升高,有显著差异.结论 VEGF治疗能明显促进大鼠部分肝脏移植术HGF、IL-6的释放.     

基于CHO细胞定点整合技术的新型抗体呈现系统的构建

目的建立一个以CHO定点整合系统为基础的高通量抗体筛选平台,筛选获得抗VEGF高亲和力突变体抗汁。方法设计并构建了基于CHO细胞定点整合系统的通用minibody展示载体,将3株亲和力已知的抗VEGF抗体（A6,A63,A657）和1个抗VEGF轻链抗体库分别呈现在CHO细胞的表面,通过Western印迹、Bia-core3000、流式细胞分析等对该展示系统进行验证和评价,并通过流式细胞分选技术对抗体库进行了细胞筛选。结果成功实现了抗VEGF抗体在CHO细胞表面的展示,流式细胞分析抗体的亲和力与Biacore测定全抗体亲和力结果一致;通过筛选获得3株抗VEGF高亲和力突变体抗体。结论建立了基于CHO定点整合技术的新型抗体库展示系统,为抗体的亲和力成熟、分子改造等突变库的构建和筛选提供了新的技术支持。     

Factors affecting visual outcomes in patients with diabetic macular edema treated with ranibizumab

Purpose

To identify factors associated with visual outcomes in patients with diabetic macular edema (DME) treated with ranibizumab (RBZ) in the Ranibizumab for Edema of the mAcula in Diabetes—Protocol 2 (READ-2) Study.

Patients and methods

Optical coherence tomography scans, fundus photographs, and fluorescein angiograms (FAs) were graded and along with baseline characteristics were correlated with month (M) 24 visual outcome of best-corrected visual acuity (BCVA) ≤20/100 (poor outcome) vs >20/100 (better outcome).

Results

Of 101 patients with a M20 visit or beyond, 27 (27%) had BCVA ≤20/100. Comparison of patients with or without poor outcome showed mean baseline BCVA of 16.8 letters (20/125) in the former compared with 30.4 letters (20/63; P<0.001). Mean change in BCVA between baseline and M24 was −2.6 letters in the poor outcome group compared with +9.8 letters (P<0.001). Foveal thickness (FTH) at M24 was 374.1 μm in the poor outcome group compared with 268.8 μm (P<0.01), a difference driven by 14 patients with mean FTH of 450.3 μm. Foveal atrophy occurred in 65% (11/17) in the poor outcome group compared with 17%(12/71, P=0.001). Persistent edema was noted in 52% (14/27) of patients with poor outcome. Laser scars near foveal center were significantly more common in patients with poor outcome who did not have edema vs those who did (78% (7/9) vs 23% (3/13) P=0.03).

Conclusion

Poor baseline BCVA (≤20/125) in DME patients predicts poor visual outcome (≤20/100) after 2 years of treatment with RBZ and/or focal/grid laser, often due to foveal atrophy and/or persistent edema.     

Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice

We examined the effect of nutritional supplements (modified Age Related Eye Disease Study (AREDS)-II formulation containing vitamins, minerals, lutein, resveratrol, and omega-3 fatty acids) on choroidal neovascularization (CNV). Supplements were administered alone and combined with intravitreal anti-VEGF in an early-CNV (diode laser-induced) murine model. Sixty mice were evenly divided into group V (oral vehicle, intravitreal saline), group S (oral supplement, intravitreal saline), group V + aVEGF (oral vehicle, intravitreal anti-VEGF), and group S + aVEGF (oral supplement, intravitreal anti-VEGF). Vehicle and nutritional supplements were administered daily for 38 days beginning 10 days before laser. Intravitreal injections were administered 48 h after laser. Fluorescein angiography (FA) and flat-mount CD31 staining evaluated leakage and CNV lesion area. Expression of VEGF, MMP-2 and MMP-9 activity, and NLRP3 were evaluated with RT-PCR, zymography, and western-blot. Leakage, CNV size, VEGF gene and protein expression were lower in groups V + aVEGF, S + aVEGF, and S than in V (all p < 0.05). Additionally, MMP-9 gene expression differed between groups S + aVEGF and V (p < 0.05) and MMP-9 activity was lower in S + aVEGF than in V and S (both p < 0.01). Levels of MMP-2 and NLRP3 were not significantly different between groups. Nutritional supplements either alone or combined with anti-VEGF may mitigate CNV development and inhibit retinal disease involving VEGF overexpression and CNV.     

VEGF is important for early liver regeneration after partial hepatectomy

BACKGROUND: The aim of the study was to determine the role of Vascular Endothelial Growth Factor (VEGF) on the microvasculature and on angiogenetic gene expression after partial hepatectomy (PH) in the rat model. METHODS: To determine the effect of exogenous and endogenous VEGF after PH, rats were subjected to 70% PH and treated either with VEGF, anti-VEGF or NaCl. Postoperatively (3-168 h), vessel density (VD), vessel diameter (VDi), and intersinusoidal space, liver body weight ratio (LBR), hepatic proliferation and biochemical markers were assessed. To further elucidate the underlying molecular mechanisms hepatic gene expression was determined by customized cDNA arrays and quantitative RT-PCR. RESULTS: In the VEGF group, VD, VDi, and LBR were significantly increased compared with anti-VEGF or controls. Blockage of endogenous VEGF led to a marked increase of biochemical markers. Anti-VEGF almost completely suppressed and VEGF markedly enhanced hepatic proliferation in the first 24 h after surgery. This was associated with a modulation of cell cycle control genes (PC4, Gadd45a, Tis21/BTG2), v-jun, and CD14 by VEGF. CONCLUSIONS: VEGF plays an important role in liver regeneration and this may be due in part through its effects on neovascularization. Whether it may, when given therapeutically, represent a strategy to optimize liver regeneration in problematic patients needs to be clarified.     

抗VEGF治疗在儿童眼底病中的应用

血管内皮生长因子(VEGF)是胚胎时期眼球发育过程中血管形成的关键介质,也是在多种眼科疾病中引起视网膜新生血管形成和血管通透性改变的重要因子。随着抗VEGF治疗在成人的应用逐渐成熟,越来越多的研究关注于抗VEGF治疗在儿童眼底病的应用,包括早产儿视网膜病变(ROP)、Coats病、家族性渗出性玻璃体视网膜病变(FEVR)、色素失禁症相关视网膜病变、镰状细胞视网膜病、视网膜母细胞瘤及各种病因引起的脉络膜新生血管等。本文将对抗VEGF在这些眼底病中的应用现状作一综述。     

玻璃体腔注射抗VEGF治疗的回顾性分析

目的：回顾分析佛山市第二人民医院眼科中心2013/2015年行玻璃体腔注射抗VEGF在眼底新生血管性疾病中的应用情况。
　　方法：回顾性分析2013-01/2015-12期间在佛山市第二人民医院眼科中心的住院患者,以手术方式为“玻璃体腔内注药术”为检索词查阅病历管理系统,排除玻璃体腔注射曲安奈德及抗生素药物的患者,就其相关疾病进行统计分析。同时查询相关疾病同年收住院患者资料并进行对比。
　　结果：3 a间共行239眼注射,男女比例接近,青年、中年及老年组间无统计学差异,3a间注射人数逐年增加。行抗VEGF( vascular endothelial growth factor )注射的相关疾病主要为脉络膜新生血管性疾病、视网膜静脉阻塞、糖尿病性视网膜病变及息肉状脉络膜血管病变,同一年度四类疾病及同种疾病不同年度行抗 VEGF 注射比率(注射/总数)有显著性统计学差异,其中脉络膜新生血管性疾病患者3a中接受注射程度最高,息肉状脉络膜血管病变则增长最快。
　　结论：抗VEGF玻璃体腔注射作为眼底新生血管性疾病新的治疗方式,正日益为患者接受。