Stickler综合征

Stickler综合征是常染色体显性遗传性胶原结缔组织疾病,又称遗传性进展性关节-眼病。本文就其临床特征、分子遗传学、分类、诊断、鉴别诊断和治疗的研究进展进行综述。     

蛋白质组学在眼科研究应用的进展

蛋白质组的研究不仅可阐述生命活动规律,也为某些疾病发生发展机理的阐明和解决途径提供理论根据。通过对个体生理或病理的蛋白质组分析比较,可以找到疾病特异性的蛋白分子,可提供疾病早期诊断的分子标志,又可成为新药物设计的分子靶点。笔者就蛋白质组学在眼科研究的应用作一综述。     

Stickler综合征

Stickler综合征是常染色体显性遗传性胶原结缔组织疾病，又称遗传性进展性关节一眼病。本就其临床特征、分子遗传学、分类、诊断、鉴别诊断和治疗的研究进展进行综述。     

血管黏附蛋白-1在眼科疾病中的研究进展

血管黏附蛋白-1(vascular adhesion protein-1,VAP-1)是一种具有黏附功能和酶催化活性双重功能的黏附分子.目前研究发现,VAP-1在炎症部位与其他黏附分子一起引导白细胞聚集、外渗,是葡萄膜炎、年龄相关性黄斑变性、糖尿病视网膜病变、结膜肿瘤等眼科疾病的重要治疗靶点.VAP-1还可作为靶分子进行活体炎症成像,这可能是一种早期诊断和描述炎症性疾病的新途径.VAP-1很可能为眼科疾病提供新的研究方向和治疗策略,本文对VAP-1在眼科疾病中的研究进展作一综述.     

我国角膜营养不良的基因研究现状

角膜营养不良是一组原发性、遗传性疾病。现代分子遗传学研究的发展使我们对角膜营养不良的认识产生了深远的影响，其在角膜营养不良的诊治中发挥了越来越重要的作用。角膜营养不良的基因研究可使我们从分子水平探讨其发病机理，明确角膜营养不良的诊断和分类。本文概述了近年来我国角膜营养不良分子遗传学的研究状况。     

伴有睑板坏死的单眼结核性结膜炎

虽然结膜性结核病在医学文献中是一个非常明确的临床疾病，但是可以与其他结膜炎混淆。分子学的诊断性组织活检可以明确诊断。我们报告了用组织病理学和分子学技术明确诊断的2例结核菌为慢性肉芽肿性结膜炎的病原。这2名患者的睑板坏死，最初怀疑为一连串睑板上积累的皮质类固醇注射造成的乳头性结膜炎。这2例病例显示迫切需要一种明确病因的全身性和合适的治疗方法。     

遗传性视网膜疾病的基因诊断

遗传性视网膜疾病具有高度的临床和遗传学异质性。单纯临床诊断对患者的病因缺少针对性信息,通过基因诊断来明确突变基因对于遗传咨询和基因治疗尤为重要。传统的基因检测技术主要包括连锁分析、直接测序法（Sanger测序）以及DNA芯片技术。新一代测序技术（next generation sequencing,NGS）兴起后已成功用于多种遗传性视网膜疾病的研究,提高了分子遗传诊断效率,降低了成本。目前我国在遗传性视网膜疾病基因诊断方面应增加人力资源培养与资金投入,制定可行的行业规范,尽早使基因诊断平台服务于临床。     

眼内淋巴瘤实验室诊断性检查的研究现状和进展

眼内淋巴瘤(IOL)是一种罕见的淋巴细胞恶性肿瘤, 组织细胞学病理检查是诊断IOL的金标准。但由于常用的玻璃体样本中淋巴瘤细胞较少且易变性, 对标本的处理及病理学专家要求较高, 容易出现假阴性的结果, 延误疾病的及时诊断及治疗。因此, 许多辅助诊断IOL的实验室检查方法应运而生, 包括流式细胞术、细胞因子白细胞介素(IL)-10和IL-6水平测定以及聚合酶链反应扩增技术等。近来基因突变分析技术也开始应用于玻璃体视网膜淋巴瘤(VRL)的诊断, 基因突变技术可能成为早期诊断IOL的方法;宏基因组深度测序技术也有助于VRL的诊断及治疗。未来有望继续推动在分子水平对IOL疾病表型的认识, 并发现新的靶向目标进行治疗、监测对治疗的反应及疾病复发情况, 为患者个性化治疗方法提供重要依据。     

关注眼病理学在眼科疾病精准诊疗中的作用

眼病理学对深入研究眼科疾病的发病机制及其发生和发展规律非常重要,可以指导眼科疾病,尤其是眼部原发肿瘤、转移瘤以及炎性疾病的临床诊断和治疗监测.眼病理学包括病理组织形态学、液态活检和分子病理学等,是临床医学和基础医学之间的重要桥梁,指导眼科疾病发病机制的研究,并对眼科学的发展起到重要的推动作用.眼科医生在眼病的诊疗过程中应重视眼病理与眼科临床辅助检查间的结合,为疾病的精准治疗提供客观依据.     

视神经炎的磁共振成像研究进展

视神经炎与中枢神经脱髓鞘关系密切,磁共振成像是目前应用最为广泛的辅助检查手段,且对神经系统疾病具有很高的诊断和研究价值.增强磁共振成像、磁化传递成像、弥散加权成像、弥散张苗成像、功能磁共振成像和分子影像因其各自独特的研究价值而成为临床视神经炎研究的重要工具.本文就近年磁共振成像住视神经炎及其相关疾病如多发性硬化,视神经脊髓炎方面的研究进展作一综述.     

What can we learn from molecular genetic analyses of inherited eye diseases?

Over the past decade, the pace of gene identification of the causes of inherited eye diseases has increased dramatically as the complete human genome information becoming available. Molecular genetic analysis establishes reliable clinical diagnostic criteria and improves the accuracy of diagnosis. We encountered two atypical cases, a patient who had only bilateral band-shaped opacities without any gelatinous prominences, and a patient who had diffuse central corneal stromal opacity without any lattice lines. The diagnosis of gelatinous drop-like dystrophy and lattice corneal dystrophy I was confirmed by molecular genetic analysis of TACSTD2 and TGFBI, respectively. We confirmed the existence of a predominantly ocular type of stickler syndrome by identifying the mutation involving exon 2 of the COL2A1 gene in a Japanese patient who had received a diagnosis of rhegmatogenous retinal detachment. We surmise that in Japan in the past, this diagnosis may have been overlooked or misdiagnosed as Wagner disease. Molecular genetic analysis is also useful for gaining a better understanding of diseases. We detected a novel FZD4 mutation in a patient with familial exudative vitreoretinopathy who exhibited peripheral avascular areas bilaterally, a dragged disk, and retinal holes unilaterally, suggesting that FZD4 may be involved in the angiogenesis of the human peripheral retina. Molecular genetic analysis of a Japanese patient with pseudoxanthoma elasticum with choroidal neovascularization revealed a homozygous nonsense mutation in the ABCC6, a member of the ABC transporter family, indicating that angioid streaks may be caused by a primary metabolic disorder. The development of rapid and comprehensive genotyping systems using state-of-the-art technology such as genotyping microarray may eventually offer unique and reliable diagnostic tools. This should then accelerate our understanding of the basic mechanisms underlying inherited eye diseases and their phenotypic variability, thus facilitating prospective diagnosis.     

眼遗传病的分子诊断

眼遗传病中有些是单基因遗传病,有些是多基因遗传病。有些眼遗传病的发病还需要特定的环境因子或表观遗传学与致病基因共同作用。致病基因和致病突变位点都存在异质性,而且不同地域或民族间有较大差异。近年来,很多与眼遗传病相关的致病基因或致病突变位点被相继报道,这些已知的致病突变位点可作为基因标记,用于眼遗传病的临床基因诊断、症状前诊断和产前诊断。本文主要关注常见眼遗传病的基因标记,介绍眼遗传病分子诊断的常用技术,并讨论如何建立较规范和完善的眼遗传病分子诊断体系。     

The role of the ophthalmologist in the management of juvenile neuronal ceroid lipofuscinosis

BACKGROUND: Neuronal ceroid lipofuscinoses (NCL) are storage diseases leading to severe somatic and mental deterioration with blindness and death. To date, there are no therapeutic options. Juvenile NCL (JNCL), also known as Batten's disease, is one of the most prevalent forms of NCL. MATERIALS AND METHODS: A 6-year-old boy with the primary diagnosis of retinitis pigmentosa was examined. The parents reported a rapid deterioration of vision during the past months. In view of this history, additional, non-ophthalmological diagnostic procedures have been performed (peripheral blood smear, molecular genetics). RESULTS: The eye examination showed a considerable reduction of visual acuity, a concentric visual field constriction, an extinguished electroretinogram and a bull's eye maculopathy. The peripheral blood smear revealed vacuolated lymphocytes. Molecular genetic investigation confirmed the diagnosis of juvenile NCL by detecting a homozygous (1-kb deletion of the CLN3-gene). CONCLUSIONS: The ophthalmologist plays a key role for an early diagnosis of juvenile NCL. An early diagnosis is important for the affected families because only then they can handle this stroke of fate.     

Ocular manifestations of genetic and developmental diseases

Although ophthalmic involvement in developmental and genetic abnormalities has been recognized for centuries, it is only recently, due to new discoveries in molecular biology, that our classification and pathophysiology of congenital eye diseases have been advanced. In the next few years these advances will increasingly influence aspects of diagnosis classification, and therapy in ophthalmology. Tests for acquired and inherited diseases in opthalmology are being revolutionized by biotechnical innovations. The molecular genetics of ocular diseases is currently undergoing changes in classification due to intense investigations using advanced biotechnology. The potential for new treatment modalities, such as gene therapy, for molecular eye diseases, once thought to be pure fiction, is now a reality. This paper will outline recent changes in classification, organization, and general knowledge regarding inherited eye diseases.     

Gene mapping of ocular diseases.

Increasing awareness of the role of genetic factors in the causation of many human eye diseases has made ocular genetics one of the fastest growing areas of ophthalmology. The objective of this paper is to present the basic principles of gene mapping and their application to ophthalmology. The techniques used to map the genome are reviewed with emphasis placed on molecular genetics. The advances in this area have already provided the major impetus to the areas of diagnosis and prevention of some genetic eye disorders. Tables are presented that list the autosomal, X-linked and mitochondrial assignment of eye genes and disorders with ocular involvement.     

Translocation of chromosomes 11 and 22 in choroidal metastatic Ewing sarcoma detected by fluorescent in situ hybridization

PURPOSE: To describe a patient with metastasis of Ewing sarcoma to the choroid and the molecular genetics of the tumor. METHODS: A 26-year-old woman with metastatic Ewing sarcoma developed large choroidal masses in the left eye and died 2 months later. Autopsy of the eyes was performed. Dual-color fluorescent in situ hybridization was used to detect genetic alteration in the ocular tumor with EWS and FLI-1 probes. RESULTS: Histopathology confirmed choroidal metastatic Ewing sarcoma. Molecular analysis showed chromosomal translocation t(11;22)(q24;q12) or EWS/FLI-1 rearrangement in the malignant cells of the eye. CONCLUSIONS: Ewing sarcoma can rarely metastasize to the uvea. Molecular detection of the t(11;22)(q24;q12) translocation in Ewing sarcoma is valuable in the differential diagnosis of small round cell tumors.     

Genetic diseases of the eye

The eye has always provided a diagnostic window for hereditary and acquired systemic diseases. Of the more than 6,000 known hereditary diseases, many are associated with changes of the visual system. Some are isolated genetic diseases of the eye, others are associated with additional ocular or systemic disorders (syndromes). In recent years, the recognition of genetic diseases as a leading cause of severe visual impairment in adults and in children has led to efforts to determine the underlying defects as well as to develop diagnostic and therapeutic molecular genetic tools. Also, education of ophthalmologists about these diseases will foster the prevention of and therapeutic approaches for genetic blindness. In this article, current knowledge on the clinical manifestations, aetiology and management of genetic diseases of the eye has been summarised.     

DNA甲基化修饰在眼科疾病发病进程中的作用研究进展

许多眼科疾病的发生发展与遗传、环境两大因素密切相关,其中表观遗传修饰是连接遗传与环境因素的重要纽带,能够通过影响基因转录或翻译影响相关基因的表达水平,在眼病的发病进程中发挥作用。DNA甲基化修饰(DNA methylation)是表观遗传修饰的重要组成部分,通常由从头甲基化、维持甲基化和去甲基化三个过程调节,在调控基因表达方面具有重要意义。目前,研究人员发现DNA甲基化修饰在角膜内皮的损伤修复、线粒体动力学调控与糖尿病视网膜病变、氧化应激反应与白内障等眼科疾病中发挥重要作用,为相关眼病的治疗提供了新的思路。本文就DNA甲基化修饰在相关眼病发展进程中的作用研究进展进行简要综述,为眼病的筛查、诊断与治疗提供新的视角与方向。     

Gene transfer in ophthalmology

Background: Research into the molecular and genetic basis of disease is continually expanding. How does the increasing knowledge about the genetic basis of eye diseases contribute to the development of new therapeutic strategies?