EphB4/EphrinB2对糖尿病视网膜病变大鼠视网膜新生血管生成的影响

目的　探讨EphB4/EphrinB2对糖尿病视网膜病变( diabetic retinopathy,DR)大鼠视网膜新生血管生成的影响。方法　取60只健康雄性SD大鼠,随机分为模型组、干预组和对照组,每组20只。模型组建立大鼠DR模型;干预组建立DR模型并于玻璃体内注射2 μL sEphB4;对照组建立DR模型并于双眼玻璃体内注射 2 μL生理盐水。分别用ADP酶染色观察视网膜新生血管形态和分布,免疫荧光双标检测EphB4/EphrinB2蛋白的表达,Western blot检测EphB4蛋白的表达。结果　各组视网膜新生血管观察结果显示,模型组和对照组大鼠视网膜毛细血管扩张、迂曲,出现微血管瘤并可见大量紊乱的新生血管,干预组视网膜血管形态接近正常,新生血管少见。模型组和对照组视网膜组织EphB4和EphrinB2蛋白呈高表达,干预组的EphB4和EphrinB2的蛋白表达量明显少于模型组和对照组,这说明 sEphB4可以有效地抑制视网膜组织EphB4和EphrinB2蛋白的表达。模型组和对照组视网膜组织EphB4蛋白表达量较高,干预组DR大鼠视网膜组织中EphB4蛋白表达量明显低于模型组和对照组。整合光密度分析的结果显示,干预组EphB4蛋白与内参β-actin 光密度值的比值（0.12±0.02）与模型组的比值（0.76±0.04）和对照组的比值（0.68±0.05）之间差异显著,均有统计学意义(均为P<0.01),而模型组和对照组差异无统计学意义(P=0.08)。结论　EphB4/EphrinB2蛋白过高表达与DR大鼠视网膜新生血管的生成密切相关,sEphB4可靶向阻断EphB4蛋白表达,并能有效抑制视网膜新生血管的生成。     

HSP27、增殖细胞核抗原在视网膜母细胞瘤中的表达

目的探讨热休克蛋白(heat shock proteins,HSP)27、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)在视网膜母细胞瘤(retinoblastoma,Rb)中的表达及其与Rb分化程度和视神经浸润的关系。方法应用鼠抗人HSP27及PCNA的单克隆抗体,采用PV9000二步法免疫组织化学方法,对36例Rb患儿和2例正常对照视网膜组织常规石蜡标本行HSP27及PCNA表达的测定,并分析它们与肿瘤分化程度及视神经浸润的关系。结果HSP27及PCNA在Rb中的表达阳性率分别为69.4%及83.3%;两指标在未分化组阳性表达高于分化组(P<0.05),两指标在视神经浸润组的阳性表达高于未浸润组(P<0.05)。Rb中HSP27的表达与PCNA的表达呈正相关(P<0.01)。结论Rb中HSP27和PCNA的表达与Rb的分化程度、视神经浸润有关。     

视网膜母细胞瘤和正常视网膜组织中基质调控蛋白表达及其意义(英文)

目的:研究视网膜母细胞瘤(RB)和正常视网膜组织中EMMPRIN、MMP1、MMP9和TIMP2表达水平及其临床病理意义和相互联系。方法:收集30例RB眼球摘除手术标本和15例正常视网膜组织标本。常规制作石蜡包埋切片,EMMPRIN、MMP1、MMP9和TIMP2染色方法均为Envision免疫组织化学法。结果:RB组织中EMMPRIN、MMP1、MMP9表达阳性率均高于正常视网膜组织(P<0.01),TIMP2则低于正常视网膜组织(P<0.01)。临床分期I期、分化型、未侵犯视神经及生存期≥2aRB病例EMMPRIN、MMP1、MMP9表达阳性率低于临床分期III期、未分化型、侵犯视神经和生存<2a病例(P<0.05或P<0.01);分化型、未侵犯视神经及生存期≥2aRB病例TIMP2表达阳性率明显高于未分化型、侵犯视神经和生存<2a病例(P<0.05或P<0.01);RB中,EMMPRIN、MMP1、MMP9表达呈高度一致性(P<0.05),TIMP2与EMMPRIN、MMP1、MMP9表达水平呈高度不一致性(P<0.05)。结论:EMMPRIN、MMP1、MMP9和TIMP2的表达水平可能是反映RB进展、侵袭能力及预后的重要标记物,它们之间存在着内在的相互调控关系。     

视网膜母细胞瘤ki-67基因蛋白表达研究

目的探讨ki-67基因蛋白在视网膜母细胞瘤中的表达及意义。方法选择11例（11只眼）视网膜母细胞瘤蜡块标本，采用免疫组织化学染色S-P法进行ki-67基因蛋白检测。结果视网膜母细胞瘤ki-67阳性表达7例（63．64％），阴性4例（36．36％）。有视神经浸润者ki-67阳性表达率高（85．71％），视网膜母细胞瘤分化差者ki-67阳性表达率高（75％）且预后差。结论ki-67在视网膜母细胞瘤中起重要的调控作用，可作为判定视网膜母细胞瘤的进展及预后的客观指标。     

视网膜母细胞瘤中血管内皮生长因子的免疫组织化学研究

目的 研究视网膜母细胞瘤(retinoblastoma,RB)中血管内皮生长因子(vascular endothelial growth factor,VEGF)表达与RB组织学分裂和浸润能力的关系。 方法 应用链霉亲和素蛋白 生物素酶标免疫组织化学方法(labell streptavidin biotin method,LSAB法)，对40例RB组织中VEGF的表达进行分析。 结果 分化型RB(13例)组织VEGF表达低于未分化型(27例)(P＜0.05); 视神经浸润组(14例)VEGF表达明显高于视神经未浸润组(26例)(P＜0.05)。 结论 VEGF表达与RB组织学分型及浸润能力相关。 (中华眼底病杂志, 1999, 15: 238-240)     

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.     

lncRNA-MEG3通过P53途径介导视网膜母细胞瘤凋亡

目的 探讨MEG3是否参与视网膜母细胞瘤的形成及其分子机制.方法 应用实时荧光定量PCR技术检测视网膜母细胞瘤组织及瘤旁正常视网膜组织标本中MEG3的表达水平;通过转染pcDNA-MEG3或siRNA-MEG3上调或干扰视网膜母细胞瘤细胞SO-RB50及HXO-RB44中MEG3的表达水平,随后用流式细胞仪检测转染后的细胞凋亡率变化,用Western blot检测转染前后P53蛋白表达水平的变化.结果 视网膜母细胞瘤组织中MEG3的表达较瘤旁正常视网膜组织出现显著下降(P=0.014).转染了pcDNA-MEG3的SO-RB50细胞MEG3表达显著增加(P =0.002),转柒了siRNA-MEG3的HXO-RB44细胞MEG3表达显著减少(P=0.004).流式细胞仪检测结果显示,MEG3表达上调后的SO-RB50细胞凋亡率显著增加(P＜0.05);干扰MEG3表达后的HXO-RB44细胞凋亡率显著减少(P＜0.05).Western blot检测结果显示,转染了pcDNA-MEG3的SO-RB50细胞中P53蛋白的表达较阴性对照组显著增加(P＜0.05),转染了siRNA-MEG3的HXO-RB44细胞中P53蛋白的表达较阴性对照组显著减少(P＜0.05).结论 视网膜母细胞瘤组织中MEG3的表达下调,且MEG3可能通过促进P53蛋白的表达诱导视网膜母细胞瘤细胞的凋亡,从而影响视网膜母细胞瘤的发生和发展.     

视网膜母细胞瘤内多种凋亡相关蛋白的检测

目的 探讨survivin在视网膜母细胞瘤(RB)中的表达及其与RB临床分期、组织分化程度及p53、bcl-2蛋白表达的关系。 方法 应用抗surv ivin、p53和bcl-2单克隆抗体，采用链霉菌抗生物素蛋白-过氧化酶免疫组织化学法对38例RB常规石蜡标本行survivin、p53和bcl-2蛋白表达的测定，对6例正常视网膜组织行survivin表达的测定。 结果 38例RB组织中20例survivin蛋白呈阳性表达，占52.6％，6例正常视网膜组织内均无survivin蛋白表达，两组比较差异有显著性的意义(P＜0.05)。survivin的阳性表达与患者的性别、临床分期、组织学分型无关(P＞0. 05)。38例RB组织中，25例p53阳性表达，18例bcl-2阳性表达，阳性表达率分别为65.8％和 47.4％。p53、 bcl-2阳性表达组中survivin阳性表达率均显著高于p53、 bcl-2阴性表达组(P均<0.05)。 结论 survivin在RB中表达上调，提示该基因可能在RB的发生发展中起一定作用；survivin、p53和bcl-2可能通过相互作用共同参与RB的发生发展。 （中华眼底病杂志，2004，20：215-217）     

PTEN和p53在视网膜母细胞瘤中的表达及临床意义

目的检测视网膜母细胞瘤(retinoblastoma,RB)组织中PTEN基因和p53基因的蛋白表达水平并探讨二者在RB发生发展中的作用以及相关性。方法采用PV-9000免疫组织化学二步法,检测40例RB组织和16例正常视网膜组织中PTEN和p53蛋白的表达,统计分析不同临床和病理阶段RB表达PTEN和p53的差异及其相关性。结果(1)PTEN在正常视网膜组织中的阳性表达率为100%,显著高于RB55%(P<0.01);PTEN蛋白的阳性表达率与临床分期、病理分型以及是否伴有视神经浸润有关(P<0·05);与性别差异无关(P>0.05)。(2)p53在正常视网膜组织中不表达,在RB组织中阳性表达率为57.5%,差异有统计学意义(P<0·05);p53蛋白的阳性表达率与临床分期、病理分型以及是否伴有视神经浸润有关(P<0.05);与性别差异无关(P>0·05)。(3)PTEN和p53在RB中的蛋白表达呈负相关(r=-0.3710,P<0.05)。结论PTEN和p53可作为判断RB恶性程度和预后的指标。PTEN可作为RB早期诊断的分子标记物之一。     

基质金属蛋白酶-1、血管内皮生长因子在视网膜母细胞瘤中的表达及意义

目的:检测基质金属蛋白酶(Matrix metalloproteinase,MMP)-1及血管内皮生长因子(Vascular endothelial growth factor,VECF)在视网膜母细胞瘤组织中表达情况,分析其与临床分级之间关系的临床意义.方法:采用免疫组化方法检测31例视网膜母细胞瘤组织MMP-1、VEGF表达,对两者的相关性进行统计学分析.结果:MMP-1、VEGF蛋白在视网膜母细胞瘤组织中呈高表达,MMP-1主要表达于肿瘤细胞胞浆或胞膜中,VEGF主要表达于肿瘤细胞胞浆中,MMP-1、VEGF表达和临床分期密切相关(P＜0.05),且其表达在不同临床分期间差异有统计学意义(P＜0.05),MMP-1、VEGF两者表达存在正相关(r=0.787,P＜0.05).结论:MMP-1、VEGF蛋白在视网膜母细胞瘤组织中呈高表达,两者表达与肿瘤临床分级密切相关,可能均参与视网膜母细胞瘤新生血管的生成,在肿瘤的浸润转移等中起重要作用.     

Segmentation and accuracy in copying and drawing: Experts and beginners

As part of an ongoing investigation into real-world copying and drawing, I recorded the eye-hand drawing strategies of 16 subjects with drawing experiences ranging from expert to novice while they copied a line drawing of a standing nude. The experts produced accurate copies whereas all the beginners produced marked inaccuracies of overall scaling, proportion and shape. Analysis of eye and hand movements showed that the experts alone segmented the original drawing into simple line sections that were copied one at a time using a direct eye-hand strategy not requiring intermediary encoding to visual memory. The results suggest that segmentation into simple lines defines the task-specific process of accurate copying, and that this process is restricted to experts, i.e. acquired through training and practice. Additional preliminary tests also suggest that a similar process may apply to drawing a model from life.     

Paraneoplastic and non-paraneoplastic retinopathy and optic neuropathy: Evaluation and management

Paraneoplastic syndromes involving the visual system are a heterogeneous group of disorders occurring in the setting of systemic malignancy. Timely recognition of one of these entities can facilitate early detection and treatment of an unsuspected, underlying malignancy, sometimes months before it would have otherwise presented, and gives the patient an increased chance at survival. We outline the clinical features, pathogenesis, and treatment strategies for the retinal- and optic nerve–based paraneoplastic syndromes: cancer-associated retinopathy; melanoma-associated retinopathy; paraneoplastic vitelliform maculopathy; bilateral diffuse uveal melanocytic proliferation; paraneoplastic optic neuropathy; and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Distinguishing these disorders from their non-paraneoplastic counterparts (e.g., autoimmune-related retinopathy and optic neuropathy, and acute zonal occult outer retinopathy) and determining appropriate systemic evaluation for the responsible tumor can be challenging. In addition, we discuss the utility and interpretation of autoantibody testing.     

Sensitivity to first- and second-order motion and form in children and adults

We compared the sensitivity of adults and children aged 3-10 years to first- and second-order motion and form. For first-order stimuli, at all ages sensitivity was better for motion than form, and motion thresholds were better at 6 Hz than at 1.5 Hz. For second-order stimuli, at all ages sensitivity was better for form than motion, and motion thresholds were better at 0.25 cyc/deg than at 1 cyc/deg. Thresholds became adult-like later for motion than for form and later for first-order than second-order stimuli. For first-order stimuli, the changes with age were larger and more protracted.     

Nodes and nodal points and lines in eyes and other optical systems

The typical stigmatic optical system has two nodal points: an incident nodal point and an emergent nodal point. A ray through the incident nodal point emerges from the system through the emergent nodal point with its direction unchanged. In the presence of astigmatism nodal points are not possible in most cases. Instead there are structures, called nodes in this paper, of which nodal points are special cases. Because of astigmatism most eyes do not have nodal points a fact with obvious implications for concepts, such as the visual axis, which are based on nodal points. In order to gain insight into the issues this paper develops a general theory of nodes which holds for optical systems in general, including eyes, and makes particular allowance for astigmatism and relative decentration of refracting elements in the system. Key concepts are the incident and emergent nodal characteristics of the optical system. They are represented by 2 × 2 matrices whose eigenstructures define the nature and longitudinal position of the nodes. If a system's nodal characteristic is a scalar matrix then the node is a nodal point. Otherwise there are several possibilities: Firstly, a node may take the form of a single nodal line. Second, a node may consist of two separated nodal lines reminiscent of the familiar interval of Sturm although the nodal lines are not necessarily orthogonal. Third, a node may have no obvious nodal line or point. In the second and third of these classes one can define mid-nodal ellipses. Astigmatic systems exist with nodal points and stigmatic systems exist with no nodal points. The nodal centre may serve as an approximation for a nodal point if the node is not a point. Examples in the Appendix , including a model eye, illustrate the several possibilities.     

Nutritional antioxidants and age-related cataract and maculopathy

Loss of vision is the second greatest, next to death, fear among the elderly. Age-related cataract (ARC) and maculopathy (ARM) are two major causes of blindness worldwide. There are several important reasons to study relationships between risk for ARC/ARM and nutrition: (1) because it is likely that the same nutritional practices that are associated with prolonged eye function will also be associated with delayed age-related compromises to other organs, and perhaps, aging in general, (2) surgical resources are insufficient to provide economic and safe surgeries for cataract and do not provide a cure for ARM, and (3) there will be considerable financial savings and improvements in quality of life if health rather than old age is extended, particularly given the rapidly growing elderly segment of our population. It is clear that oxidative stress is associated with compromises to the lens and retina. Recent literature indicates that antioxidants may ameliorate the risk for ARC and ARM. Given the association between oxidative damage and age-related eye debilities, it is not surprising that over 70 studies have attempted to relate antioxidant intake to risk for ARC and ARM. This article will review epidemiological literature about ARC and ARM with emphasis on roles for vitamins C and E and carotenoids. Since glycation and glycoxidation are major molecular insults which involve an oxidative stress component, we also review new literature that relates dietary carbohydrate intake to risk for ARC and ARM. To evaluate dietary effects as a whole, several studies have tried to relate dietary patterns to risk for ARC. We will also give some attention to this emerging research. While data from the observational studies generally support a protective role for antioxidants in foods or supplements, results from intervention trials are less encouraging with respect to limiting risk for ARC/ARM prevalence or progress through antioxidant supplementations, or maintaining higher levels of antioxidants either in diet or blood. Without more information it is difficult to parse these results. It would be worthwhile to determine why the various types of studies are not yielding similar results. However, there are many common insults and mechanistic compromises that are associated with aging, and proper nutrition early in life may address some of these compromises and provide for extended youthful function later in life. Indeed, proper nutrition, possibly including use of antioxidant supplements for the nutritionally impoverished, along with healthy life styles may provide the least costly and most practical means to delay ARC and ARM. Further studies should be devoted to identifying the most effective strategy to prevent or delay the development and progress of ARC/ARM. The efforts should include identifying the right nutrient(s), defining useful levels of the nutrient(s), and determining the age when the supplementation should begin.     

Ethics and optometry: concepts and applications

Ethics refers both to the study of behaviour, and moral principals. The related concepts of justice and law are also relevant to optometry. A profession typically claims specialist knowledge and ethical behaviour – putting the interests of clients above its own. However, professional codes fail as ethical directives, and their goals are questioned. Beginning with broad principles, institutional ethics and issues of general health care provision are considered, and applications to optometry are made. Ethical theory can guide us in interacting with our patients, utilising resources and ordering priorities. The conservative approach to consumerism and advertising is defended on the basis of protecting public and professional interests. Ethical behaviour can be fostered, and this process should begin in undergraduate education.     

Exogenous attention and color perception: performance and appearance of saturation and hue

Exogenous covert attention is an automatic, transient form of attention that can be triggered by sudden changes in the periphery. Here we test for the effects of attention on color perception. We used the methodology developed by Carrasco, Ling, and Read [Carrasco, M., Ling, S., & Read, S. (2004). Attention alters appearance. Nature Neuroscience, 7 (3) 308-313] to explore the effects of exogenous attention on appearance of saturation (Experiment 1) and of hue (Experiment 2). We also tested orientation discrimination performance for single stimuli defined by saturation or hue (Experiment 3). The results indicate that attention increases apparent saturation, but does not change apparent hue, notwithstanding the fact that it improves orientation discrimination for both saturation and hue stimuli.     

Aberration and contrast sensitivity comparison of aspherical and monofocal and multifocal intraocular lens eyes

BACKGROUND: Higher-order aberrations and contrast sensitivity were evaluated in patients who underwent phacoemulsification cataract extraction followed by implantation of aspherical, monofocal or multifocal intraocular lens (IOL) replacements. METHODS: In this comparative trial, 124 patients with an average age of 66.8+/-5.2 years and their 124 eyes were randomly divided into three surgical implantation groups to receive one of three types of IOLs in replacement of cataract lenses. The patients of group 1 were given an aspherical IOL Z9001 (AMO, Santa Ana, CA, USA) replacement, and group 2 was implanted a monofocal IOL SA60AT (Alcon, Fort Worth, TX, USA) and group 3 the multifocal IOL SA40N (AMO). Post-surgical best-corrected visual acuity, corneal aberrations, total ocular aberrations, pupil diameters, capsulorhexsis sizes and contrast sensitivity were measured and compared. RESULTS: There was no statistical difference for mean best-corrected visual acuity, pupil diameter, curvilinear capsulorhexis size and corneal aberration among the three groups. For the spherical aberration, fourth-order higher-order aberration and total ocular higher-order aberration, the SA40N group was higher than the SA60AT group and the SA60AT group was higher than the Z9001 group, and the differences between the three groups were statistically significant for these measurements. Contrast sensitivity was higher for the Z9001 group than the SA60AT group and the SA60AT group was higher than the SA40N group, and the difference was statistically significant in all the spatial frequencies of 3, 6, 12 and 18. CONCLUSIONS: Although the multifocal IOL can provide near vision, it can increase higher-order aberration and negatively influence contrast sensitivity. However, the aspherical IOL can reduce aberration and improve contrast sensitivity as compared with the monofocal IOL.