炎症因子与糖尿病视网膜病变相关性研究进展

糖尿病视网膜病变( diabetic retinopathy,DR)是20 ～ 70岁人群首要的致盲性眼病,是目前眼科研究的重点和热点.越来越多的研究证明炎症因子参与了DR的发生发展,这为研究DR的发病机制提供了新的线索,同时为临床利用抗细胞因子药物防治DR的发生发展提供新的研究方向.本文就目前炎症因子与DR相关性的研究讲展讲行综述.     

Statistical study of factors related to occurrence and progression of retinopathy in extremely premature infants: especially clinical changes in PaCO2 and pH

Out of 39 premature infants admitted to the NICU in Toho University Hospital from January 1983 to December 1985 and surviving for 2 months after birth, 22 extremely premature infants who were closely matched in terms of gestational age and body weight at birth were divided into 4 groups (operated group, non-operated A group, non-operated B group and broncho-pulmonary dysplasia (BPD) group) to assess the effect of respiratory management on retinopathy of prematurity (ROP). ROP occurred at a high frequency in extremely premature infants weighing less than 1,000 g. In most of the infants who underwent operation (cryocauterization), PaCO2 values were low for 1 month after birth, whereas pH tended to rise. In the non-operated B group, PaCO2 was almost normal, and pH tended toward acidosis. BPD, which causes severe respiratory disturbance, was observed in 4 cases, 3 of whom showed a rise in PaCO2 within 1 month after birth, but mild ROP. Thus, it was considered that PaCO2 and pH exacerbated ROP.     

Influence of polymorphisms in VEGF, ACE, TNF and GST genes on the susceptibility to retinopathy of prematurity among Chinese infants

AIM: To investigate common polymorphisms in VEGF, ACE, TNF and GST genes with retinopathy of prematurity (ROP) risk among Chinese infants. METHODS: Nine polymorphisms in the above genes were genotyped on 724 advanced cases of ROP and 878 prematurely-born infants of low birth weight who were without any ophthalmologic disease. The frequencies of the polymorphisms were compared between cases and controls to identify the association present, if any. RESULTS: Of the nine polymorphisms, only two showed significant associations: ACE insertion deletion (ID) polymorphism (P=0.031) and TNF -308G/A polymorphism (P<0.001). The former was associated with a reduced ROP risk [ID genotype, adjusted OR (aOR): 0.603, 95%CI: 0.427-0.893, P=0.034; DD genotype, aOR: 0.468, 95%CI: 0.229-0.626, P=0.002], while the latter showed an increased risk (GA genotype, aOR: 1.956, 95%CI: 1.396-2.465, P<0.001; AA genotype, aOR: 2.809, 95%CI: 1.802-4.484, P<0.001). The association was also noted at the allele level (ACE D allele aOR: 0.698, 95%CI: 0.294-0.883, P<0.001; TNF -308A allele aOR: 1.776, 95%CI: 1.446-2.561, P<0.001). CONCLUSION: The ACE ID polymorphism can protect against ROP development while the TNF -308G/A can increase the risk of the disease among Chinese infants.     

Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality

Retinal microvascular abnormalities, such as generalized and focal arteriolar narrowing, arteriovenous nicking and retinopathy, reflect cumulative vascular damage from hypertension, aging, and other processes. Epidemiological studies indicate that these abnormalities can be observed in 2-15% of the nondiabetic general population and are strongly and consistently associated with elevated blood pressure. Generalized arteriolar narrowing and arteriovenous nicking also appear to be irreversible long-term markers of hypertension, related not only to current but past blood pressure levels as well. There are data supporting an association between retinal microvascular abnormalities and stroke, but there is no convincing evidence of an independent or direct association with atherosclerosis, ischemic heart disease, or cardiovascular mortality. New computer-related imaging methods are currently being developed to detect the presence and severity of retinal arteriolar narrowing and other microvascular characteristics. When reliably quantified, retinal microvascular abnormalities may be useful as risk indicators for cerebrovascular diseases.     

ACE2 and TMPRSS2 are expressed on the human ocular surface,suggesting susceptibility to SARS-CoV-2 infection

PurposeConjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection.MethodsWe analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2.ResultsAcross all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as weak or focal expression in the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, Western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2.ConclusionsTogether, these results suggest that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.     

视网膜母细胞瘤组织芯片中PTEN、mdm2、p53表达及与组织病理特征关系的研究

目的 探讨视网膜母细胞瘤组织芯片中PTEN,murine double minute 2(mdm2)及p53蛋白的表达及与肿瘤临床组织病理特征的关系.设计实验性研究.研究对象 64例视网膜母细胞瘤和6例正常视网膜组织.方法 免疫组化方法检测视网膜母细胞瘤组织芯片和正常视网膜组织石蜡标本中PTEN,mdm2及p53的表达情况,将肿瘤分为球后视神经受侵袭组和球后视神经未受侵组,检测两组间mdm2及p53表达差异,并结合肿瘤的组织病理学特征进行综合分析.主要指标视网膜母细胞瘤组织芯片中PTEN,mdm2和p53表达率.结果 视网膜母细胞瘤中PTEN,mdm2与p53的阳性表达率分别为53.13%,48.43%和53.13%.球后视神经受侵袭组较球后视神经未受侵组mdm2(P=0.027)及p53(P=0.017)表达均明显增高.视网膜母细胞瘤中PTEN与p53表达呈负相关(r=-0.384,P=0.045),mdm2与p53蛋白表达呈正相关(r=0.281,P=0.018).结论 视网膜母细胞瘤中mdm2和p53的过度表达与视神经侵袭程度存在一定相关性.mdm2及p53蛋白的检测可能成为视网膜母细胞瘤恶性程度的参考指标.     

白内障晶状体上皮细胞Bcl-2Bax表达的增龄性研究

目的 探讨随着年龄的增长白内障晶状体上皮细胞Bcl-2、Bax的基因表达与白内障发生的关系,及其在白内障发生发展中的作用机制.方法 选取行超声乳化白内障手术的患者91例91只眼,取晶状体前囊膜.根据年龄分为3组,即Ⅰ组为≤30岁的患者11例,Ⅱ组为31～60岁的患者30例,Ⅲ组为≥61岁的患者50例.采用链霉菌亲生物素蛋白-过氧化物酶标免疫组织化学法(streptavidin-peroxidase,SP)染色,镜下检测三个不同年龄组白内障患者晶状体上皮细胞Bcl-2基因蛋白与Bax基因蛋白的表达情况.结果 Ⅰ、Ⅱ、Ⅲ组Bcl-2基因表达分别为89%、60%、0.5%,Bax基因表达分别为0、11%、91%.各项指标经统计学分析具有统计学意义(P<0.05).结论 随着年龄的增长白内障晶状体上皮细胞Bcl-2基因表达逐渐降低,Bax基因表达逐渐增高,为在基因水平上治疗白内障提供了理论依据.

Abstract：

Objective To evaluate the relationship between cataract lens epithelial cell and Bcl-2, Bax expression with increasing age in patients, and to investigate the role of Bcl-2 and Bax expression in the occurrence and progression of human lens epithelial cells of cataract.Methods Ninety-one patients (91 eyes) who were done phacoemulsification for cataract were selected and took anterior capsule of lens.The cataract patients were divided into three groups according to age: 11 cases of less than 30 years of age in group Ⅰ , 30 cases of aged 31-60 in group Ⅱ, 50 cases more than 61 years of age in group Ⅲ.The expression of Bcl-2 and Bax in lens epithelial cells of cataract from three different age groups of cataract patient was detected by the immunohistochemical streptavidin-peroxidase (SP) method.Results The Bcl-2 gene expression in group Ⅰ , Ⅱ, and Ⅲ was 89%, 60% and 0.5% respectively, the Bax gene expression was 0, 11% and 91% respectively.The difference had the statistical significance between 3 groups (P <0.05).Conclusions The genes expression of Bcl-2 in human lens epithelial cells of cataract is gradually decreasing with age increasing, while the genes expression of Bax is gradually increasing with age increasing.It provides an important theoretical basis to treat of cataract at the gene level.     

糖尿病视网膜病变易感性与相关基因多态性研究进展

糖尿病视网膜病变(DR)是一种多因素介导的疾病,目前公认DR是由慢性高血糖引起的代谢环境异常所致,但其发生受遗传因素的调控,被认为是人类复杂疾病的经典案例,可归因于遗传因素、环境因素及其之间的相互作用结果。遗传学对DR发生发展的研究已取得了一定成果,但具体的致病基因及其发病机制仍尚未明确。本研究针对目前已确定的潜在DR易感基因及其多态性进行综述,为进一步研究DR致病基因及其发病机制提供参考。     

兔角膜基质细胞培养及对病毒敏感性的实验研究

目的 研究体外培养兔角膜基质细胞对病毒的敏感性。方法 采用微量细胞病变法,观察体外培养的兔角膜基质细胞对单纯疱疾病毒Ⅰ、Ⅱ型(herpes simplex virus Ⅰ、Ⅱ,HSV-Ⅰ、Ⅱ)、腺病毒3型(adenovirus type 3,Ad3)、滤疱性口腔炎病毒(vesicularstomatitis virus,VSV)等4种病毒的敏感性。结果 病毒接种于兔角膜基质细胞48h,HSV-Ⅰ和HSV-Ⅱ效价(TCID_(50))分别为64×10~(-3)、128×10~3,VSV效价(TCID_(50))为10~(-2),Ad3不引起细胞病变。结论 兔角膜基质细胞对HSV-1、HSV-2均敏感,对VSV、Ad3不敏感。