Sirtuins在年龄相关性白内障中的相关作用研究进展

sirtuins家族(芋类组蛋白去乙酰化酶)作为表观遗传学的分支之一,近年来备受瞩目。 SIRT1作为sirtuins家族中最知名的的成员已被验证参与了多种年龄相关性疾病。而SIRT1在年龄相关性白内障形成中所起到的作用也越来越受到关注。现就将SIRT1在年龄相关性白内障中的作用的研究进展进行简要概述。     

PDT联合ranibizumab玻璃体腔注射治疗年龄相关性黄斑变性合并CNV

目的：观察 PDT 联合玻璃体腔注射 ranibizumab (雷珠单抗)治疗老年性黄斑变性脉络膜新生血管( choroidal neovascularization,CNV)的疗效。
　　方法：将符合纳入标准,经吲哚青绿脉络膜血管造影(indocyanine green angiography, ICGA)、光学相干断层扫描( optical coherence tomography, OCT)检查确诊为黄斑区脉络膜新生血管( CNV)患者27例27眼,经PDT治疗后3~7 d内行 ranibizumab 玻璃体腔注射。观察治疗后1,3,6 mo、末次随访时行最佳矫正视力、FFA、ICGA、OCT 检查及有无并发症发生情况。
　　结果：最佳矫正视力提高17眼(63%),最佳矫正视力稳定6眼(22%),最佳矫正视力下降4眼(15%)。27例27眼治疗前平均渗漏面积为1005.69±105.47μm,治疗后1,3mo后平均875.54±103.27,423.37±79.68μm,与治疗前比较差异有统计学意义(P<0.01),视网膜黄斑中央厚度27例27眼治疗前平均厚度为485.58±122.59μm,治疗后1,3mo后平均398.84±105.32,297.74±89.18μm,与治疗前比较差异有统计学意义(P<0.01)。
　　结论：PDT 封闭 CNV 后,联合玻璃体内腔内注射ranibizumab,有效阻断新生血管复发,减少PDT再次治疗次数和并发症,可提高治疗效果。     

视网膜色素上皮细胞氧化应激相关microRNA的鉴定

目的：应用miRNA表达谱芯片筛选视网膜色素上皮细胞与氧化应激相关的miRNA,为更加全面深入地研究年龄相关性黄斑病变(age-related macular degeneration,AMD)发生的分子机制提供新的思路。

方法：培养D407细胞,分别使用100、200、400μmol/L H₂O₂处理细胞24h后,Trizol试剂抽提细胞总RNA,使用Exiqon miRCURY LNA^TM microRNA表达谱芯片(miRBase 16.0数据库)检测不同浓度处理后D407细胞miRNA的表达差异,并将不同浓度处理后的变化进行聚类分析。使用Stem loop realtime PCR对芯片结果进行验证,并运用生物信息学方法预测差异miRNA调控的靶基因。

结果：芯片所包含的1 425个已知miRNA中,共有367个在不同浓度H₂O₂处理后表达发生变化。通过Treeview软件进行聚类分析发现miR-31等17个miRNA随H₂O₂浓度的升高呈现逐渐降低的趋势,miR-206等7个则逐渐升高。PCR验证显示芯片结果准确性较好。

结论：H₂O₂作用前后RPE的miRNA表达存在明显差异,miRNA作为转录后水平的调节分子,参与了细胞氧化应激反应,可能在AMD的发生发展中起有重要作用。     

视网膜血管瘤样增生和湿性年龄相关性黄斑病变的鉴别

视网膜血管瘤样增生(retinal angiomatous proliferation,RAP)是湿性年龄相关性黄斑变性(age-related macular degeneration,AMD)的一种特殊类型,临床一般分三期,晚期有新生血管形成,但与起源于脉络膜的新生血管不同,多数学者认为RAP的新生血管起源于视网膜深层毛细血管网。目前对RAP和湿性AMD两者到底是同一种疾病的不同亚型还是独立的两种疾病还存在争议,由于两者的病程、预后及治疗存在差异,因此临床鉴别诊断十分重要。近年来,随着吲哚菁绿血管造影(indocyanine green angiography,ICGA)技术和新一代光学相干断层扫描(optical coherence tomography,OCT)技术的应用,对RAP和湿性AMD的鉴别取得了显著进步。本文就两者的临床表现、自然病程、治疗方法及预后等方面做一综述。     

康柏西普玻璃体腔注射治疗湿性年龄相关性黄斑变性

目的：观察康柏西普玻璃体腔注射治疗湿性年龄相关性黄斑变性的临床疗效。

方法：将确诊的60例湿性年龄相关性黄斑变性的患者,根据随机数字表法分为治疗组和对照组各30例。治疗组注射康柏西普0.05mL,对照组注射曲安奈德0.1mL。在治疗前及治疗后1d,1、3mo采用标准视力表对患者进行最佳矫正视力(BCVA)检查; 用光学相干断层扫描仪(OCT)检测黄斑中心凹视网膜厚度。并观察患者治疗后1d,1、3mo内出现的并发症情况,包括前房炎性反应、角膜水肿、高眼压等。

结果：治疗组治疗后1d,1、3mo视力提高明显好于对照组(P<0.05)。治疗组治疗后1d,1、3mo的黄斑中心凹视网膜厚度明显低于对照组(P<0.05)。治疗组和对照组治疗后1d,1、3mo均未出现眼部严重并发症。

结论：康柏西普玻璃体腔注射治疗湿性年龄相关性黄斑变性可以提高疗效。     

三种不同方法测量年龄相关性白内障患者前房深度的比较

目的：：比较光学生物学测量仪( IOL Master )、接触式和浸润式A超对前房深度( anterior chamber depth,ACD)的测量结果,分析三种测量方法是否存在差异及其一致性。方法：选取2013-07/10于我院诊断为年龄相关性白内障患者58例98眼术前分别进行IOL Master、接触式A超和浸润式A超的ACD测量,应用方差分析对三种方法的测量结果差异进行比较,应用Blant-Altman分析法比较其一致性。结果：IOL Master 测量 ACD 为2.31~3.90(平均3.03±0.38) mm;接触式 A 超测量 ACD 为1.51~4.06(平均2.88±0.56)mm;浸润式A超测量ACD为1.99~4.17(平均3.17±0.38)mm。 IOL Master和接触式A超的ACD测量值差异有统计学意义( P=0.022<0.05)。 IOL Master和浸润式A超ACD测量值差异有统计学意义( P=0.031<0.05)。接触式A超与浸润式A超ACD测量值差异有统计学意义(P=0.000<0.05)。三种方法相互间一致性均较差。结论：三种方法测量白内障患者ACD时,浸润式A超测得结果最大,IOL Master次之,接触式A超测得结果最小,三者相互间一致性均较差,临床不建议相互替代。     

康柏西普治疗老年性黄斑变性的研究现状

老年性黄斑变性( AMD)已经成为发达国家老年人致盲的主要原因之一。随着AMD患者的逐年增加,这也成为眼科防盲研究中重要的课题之一。其病因并不完全清楚,但许多研究表明血管内皮生长因子( VEGF)在其发病中起了重要作用。随着抗VEGF药物的研发与应用,目前已有多种药物应用于该病,本文主要介绍康柏西普在老年性黄斑变性中的应用。     

Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases

Vision is the sense that we use to navigate the world around us. Thus it is not surprising that blindness is one of people's most feared maladies. Heritable diseases of the retina, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world, collectively affecting as many as one-third of all people over the age of 75, to some degree. For decades, scientists have dreamed of preventing vision loss or of restoring the vision of patients affected with retinal degeneration through drug therapy, gene augmentation or a cell-based transplantation approach. In this review we will discuss the use of the induced pluripotent stem cell technology to model and develop various treatment modalities for the treatment of inherited retinal degenerative disease. We will focus on the use of iPSCs for interrogation of disease pathophysiology, analysis of drug and gene therapeutics and as a source of autologous cells for cell transplantation and replacement.     

Effects of Vitreomacular Traction on Ranibizumab Treatment Response in Eyes with Neovascular Age-related Macular Degeneration

PurposeTo investigate the effects of vitreomacular traction (VMT) on ranibizumab treatment response for neovascular age-related macular degeneration (AMD).MethodsA retrospective review of 85 eyes of 85 patients newly diagnosed with neovascular AMD was conducted. Patients were eligible if they had received more than three consecutive monthly ranibizumab (0.50 mg) treatments and ophthalmic evaluations. Patients were classified into a VMT (+) group or VMT (-) group according to optical coherence tomography imaging. Best corrected visual acuity and central retinal thickness (CRT) measurements were obtained at three and six months after initial injection.ResultsOne month after the third injection, mean visual acuity (VA) increases of 6.36 and 9.87 letters were observed in the VMT (+) and VMT (-) groups, respectively. The corresponding mean CRT values decreased by 70.29 µm and 121.68 µm, respectively. A total 41 eyes were identified as eligible for a subsequent fourth injection; 71.1% of patients (27 eyes) in the VMT (+) group but only 29.8% of patients in the VMT (-) group needed a subsequent fourth injection. Follow-up was extended to six months for 42 of the 85 enrolled patients (49.4%). The trends in VA and optical coherence tomography were found to be maintained at six-month follow-up.ConclusionsVA and CRT appeared to be more improved after ranibizumab treatment in the VMT (-) group compared to the VMT (+) group. VMT might antagonize the effect of ranibizumab treatment in a subpopulation of AMD patients.     

Association between SERPING1 rs2511989 polymorphism and age-related macular degeneration: Meta-analysis

AIM: To investigate the association between SERPING1 rs2511989 (G>A) polymorphism and age-related macular degeneration (AMD). METHODS: A number of electronic databases (up to July 15, 2014) were searched independently by two investigators. A Meta-analysis was performed on the association between SERPING1 rs2511989 polymorphism and AMD. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. RESULTS: Eight studies with 16 cohorts consisting of 9163 cases and 6813 controls were included in this Meta-analysis. There was no significant association between rs2511989 polymorphism and AMD under all genetic models in overall estimates (A vs G: OR= 0.938, 95%CI =0.858-1.025; AA vs GG:OR =0.871, 95%CI =0.719-1.056; AG vs GG: OR =0.944, 95%CI =0.845-1.054; AA+AG vs GG: OR =0.927, 95% CI =0.823-1.044; AA vs AG+GG: OR =0.890, 95%CI =0.780-1.034). Cumulative Meta-analyses also showed a trend of no association between rs2511989 polymorphism and AMD as information accumulated by year. Subgroup analysis and Meta-regression analysis indicated that age-matching status was the main source of heterogeneity. Sensitivity analysis found the results in overall comparisons and subgroup comparisons of white subjects under the allele model were found to have significantly statistical differences after studies deviating from Hardy-Weinberg equilibrium (HWE) were excluded (overall: OR=0.918, 95%CI = 0.844-0.999, P =0.049; whites: OR =0.901, 95%CI = 0.817-0.994, P =0.038). However, the results were not sufficiently robust for further sensitivity analysis and statistical differences disappeared on applying Bonferroni correction (with a significance level set at 0.05/25). CONCLUSION: This Meta-analysis indicates that SERPING1 rs2511989 polymorphism and AMD tend to have no association with each other. Age matching status is a big confounding factor, and more studies with subtle designs are warranted in future.