Genetics of the corneal dystrophies: what we have learned in the past twenty-five years

PURPOSE: To indicate important changes in our understanding of the corneal dystrophies. METHODS: A review of the literature of the last quarter of a century. RESULTS: The earliest clinical classifications of the corneal dystrophies were based on the application of clinical, biological, histochemical, and ultrastructural methods. Since then, the first great impetus to our understanding has come from the application of techniques to map disorders to specific chromosome loci, using polymorphic markers. More recently, using candidate gene and related approaches, it has been possible to identify genes causing several of the corneal dystrophies and the mutations responsible for their phenotypic variation. A notable success has been to show that several important "stromal" dystrophies result from mutations in the gene beta ig-h3, which encodes for the protein keratoepithelin (beta ig-h3). CONCLUSIONS: For the corneal dystrophies, as with other inherited disorders, there is room for two sorts of classification system, one based mainly on clinical presentation and the other on an up-to-date understanding of the genetic mechanisms. They are not mutually exclusive. Some developmental corneal disorders are also discussed.     

The past twenty-five years in eye banking

PURPOSE: This review of milestones and challenges in eye banking describes efforts made by dedicated eye bankers to ensure the quality and quantity of corneal tissue for corneal blind patients over the last 25 years. METHODS: This account is the result of the recollection of the author, discussions with eye bankers, and a review of the literature, public documents, and Eye Bank Association of America (EBAA) records. RESULTS: A measure of the success of eye banking is the fact that corneal transplant surgery is now scheduled as an elective procedure. Corneal tissue has also enjoyed a stellar safety record. This is due in part to the establishment of comprehensive medical standards by the EBAA, the accreditation of eye banks, and the training and certification of eye bank technicians. CONCLUSION: Advancements in eye banking over the last 25 years have improved the quality of life of several hundred thousand corneal blind persons in this country. More efforts must be made in the future to eliminate corneal blindness internationally.     

Molecular underpinnings of corneal angiogenesis: advances over the past decade

The cornea is maintained in an avascular state by maintaining an environment whereby anti-angiogenic factors take the upper hand over factors promoting angiogenesis. Many of the common pathologies affecting the cornea involve the disruption of such equilibrium and the shift towards new vessel formation, leading to corneal opacity and eventually-vision loss. Therefore it is of paramount importance that the molecular underpinnings of corneal neovascularization (CNV) be clearly understood, in order to develop better targeted treatments. This article is a review of the literature on the recent discoveries regarding pro-angiogenic factors of the cornea (such as vascular endothelial growth factors, fibroblast growth factor and matrix metalloproteinases) and anti-angiogenic factors of the cornea (such as endostatins and neostatins). Further, we review the molecular underpinnings of lymphangiogenesis, a process now known to be almost separate from (yet related to) hemangiogenesis.     

The evolution of lamellar grafting techniques over twenty-five years

The history of lamellar keratoplasty (LK) surgery spans over 100 years, and the advantages of lamellar surgery have long been known. The surgery is usually used for tectonic purposes; however, new techniques and technology over the past 25 years have expanded the applications of LK in optical rehabilitation. Instrumentation such as viscoelastics, diamond knives, ultrasonic pachymetry, artificial anterior chambers, advanced microkeratomes, and the excimer laser have enhanced our ability to work more safely in the tedious microsurgical environment of the lamellar procedure. Advances in surgical techniques such as deep lamellar anterior keratoplasty and deep lamellar endothelial keratoplasty have expanded the application of lamellar surgery to endothelial replacement and have achieved visual results approaching those of penetrating keratoplasty while reducing the rate of rejection and improving the long-term graft stability. As research continues, LK promises to be an increasingly important option for the corneal surgeon.     

组织工程角膜内皮移植的研究进展

随着组织工程技术和细胞工程技术的不断发展,组织工程角膜的研究已经取得一定进展,其中体外培养角膜内皮细胞技术的成熟为组织工程角膜内皮移植奠定了基础.通过将不同来源的角膜内皮种子细胞种植于合适的载体上得到重构的角膜内皮,应用其取代失代偿角膜内皮细胞,这种技术的成熟将会为角膜内皮损害而致盲患者带来新的希望.     

Visual attention: the past 25 years

This review focuses on covert attention and how it alters early vision. I explain why attention is considered a selective process, the constructs of covert attention, spatial endogenous and exogenous attention, and feature-based attention. I explain how in the last 25 years research on attention has characterized the effects of covert attention on spatial filters and how attention influences the selection of stimuli of interest. This review includes the effects of spatial attention on discriminability and appearance in tasks mediated by contrast sensitivity and spatial resolution; the effects of feature-based attention on basic visual processes, and a comparison of the effects of spatial and feature-based attention. The emphasis of this review is on psychophysical studies, but relevant electrophysiological and neuroimaging studies and models regarding how and where neuronal responses are modulated are also discussed.     

Eye movements: the past 25 years

This article reviews the past 25 years of research on eye movements (1986-2011). Emphasis is on three oculomotor behaviors: gaze control, smooth pursuit and saccades, and on their interactions with vision. Focus over the past 25 years has remained on the fundamental and classical questions: What are the mechanisms that keep gaze stable with either stationary or moving targets? How does the motion of the image on the retina affect vision? Where do we look - and why - when performing a complex task? How can the world appear clear and stable despite continual movements of the eyes? The past 25 years of investigation of these questions has seen progress and transformations at all levels due to new approaches (behavioral, neural and theoretical) aimed at studying how eye movements cope with real-world visual and cognitive demands. The work has led to a better understanding of how prediction, learning and attention work with sensory signals to contribute to the effective operation of eye movements in visually rich environments.     

The corneal endothelium in vivo: its response to mild trauma

Changes in the specular microscopical appearance of the corneal endothelium are induced by the application of glycerin drops, in clinically used concentrations, to the epithelial surface of living rabbit corneas. Many of the affected cells appear to recover but a large number fall away and are replaced by the spread of neighbouring cells, eventually to leave no trace of their loss. The processes involved are described as seen and photographed in vivo with a modified, “roving”, specular microscope over prolonged periods of observation.The reduction in cell population results in no demonstrable loss of functional efficiency of the endothelium as evaluated by the temperature reversal phenomenon in vitro, after a period of cooling the eyes to 4°C. However, urethane anaesthesia is shown to be suspect in interfering with the pump-leak mechanisms of the endothelium.     

The evolution of antiviral therapy for external ocular viral infections over twenty-five years

PURPOSE: To review the past 25 years of the evolution of antiviral therapy for the treatment of common external ocular viral infections (herpes simplex virus type 1, varicella-zoster virus, and adenovirus). METHODS: A broad-based literature review in the fields of virology, antiviral research, and ophthalmology will be carried out. The pathogenesis of the major external ocular viral infections and history of antiviral development will be cited. Important conceptual breakthroughs as well as historical landmarks will be emphasized. RESULTS: The successful development of effective antivirals to treat the most common external ocular viral infections have dramatically reduced morbidity and sight loss. The immune pathogenesis of herpetic stromal keratitis is better understood. CONCLUSIONS: Remarkable progress in the development of antiviral therapy has occurred over the past quarter century. Future needs include improved antivirals and immunomodulators and vaccines to prevent and treat herpetic ocular infections and adenovirus keratoconjunctivitis.     

Recent advances in corneal stromal dystrophies

Newer biochemical, immunohistochemical, and cell culture techniques have been used to investigate metabolic abnormalities in corneal stromal dystrophies. Organ cultures of macular corneal dystrophy (MCD) have shown a defect in the synthesis of keratan sulphate proteoglycan. Alterations in corneal stromal glycoconjugates have also been detected using biotinylated lectins. An absence of normal keratan sulphate proteoglycan has been shown in the blood of patients with MCD. Granular corneal dystrophy (GCD) is associated with increased phospholipid, as shown by biochemical analysis and staining with Luxol-fast blue. Immunohistochemical stains revealed reactivity with antibodies against microfibrillar protein at the edges of the deposits. Clinically, recently described early features of lattice corneal dystrophy (LCD) include discrete ovoid subepithelial opacities, a diffuse central anterior stromal haze, and anterior stromal dots and filamentary lines. Early clinical recognition of these corneal genetic disorders, with appropriate studies to define their nature and possible pathogenetic mechanisms, are important in expanding our knowledge of this disease spectrum.     

角膜营养不良的分子遗传学研究进展

角膜营养不良是一种遗传性疾病,随着分子遗传学研究技术的发展,对引起各类角膜营养不良的致病原因有了进一步的认识,并确定了部分角膜营养不良的相关遗传基因和突变位点。本文对新的研究进展进行了综述。     

microRNA在角膜新生血管中的研究进展

角膜新生血管（ corneal neovascularization）是影响角膜透明度的主要因素之一,也是同种异体角膜移植术后发生排斥反应的高危因素,因此角膜新生血管形成的调控已成为研究热点。 microRNA是一组内源性非编码小分子RNA,在调控多种生物进程中起重要作用。近年来研究表明, microRNA与角膜新生血管形成有着紧密联系,本文将对目前的研究情况进行综述。     

角膜新生血管治疗的研究进展

角膜新生血管( corneal neovascularization ,CNV)是由维持角膜无血管的平衡因素被破坏,角膜缘的毛细血管侵入无色清亮的角膜组织导致。 CNV是国内较常见的致盲眼病之一,近年来,尽管免疫学、细胞分子生物学和药理学等学科发展让我们对CNV的发病因素及治疗的认识有不少突破,但病因多样缺乏总结,且迄今为止,对CNV的治疗尚无特效疗法。本文将简要阐述CNV的病因、发病机制,着重总结CNV的治疗进展。     

新生淋巴管与角膜移植排斥的研究进展

角膜新生淋巴管构成了角膜免疫反应的传入弧,在免疫反应中发挥了重要作用。由于新生淋巴管的出现破坏了免疫机制使角膜移植术后排斥反应发生率升高。随着淋巴管内皮标记物的相继出现和对淋巴管生成因子的研究深入,众多学者对角膜淋巴管在角膜免疫排斥反应机制、治疗和预防等方面进行了大量研究,通过抑制新生淋巴管提高植片存活率。     

角膜内皮细胞培养的研究进展

角膜内皮功能失代偿引起的失明可通过角膜移植来治疗.人们通过体外培养角膜内皮细胞并使其增殖,进行角膜内皮细胞移植和角膜组织工程学研究.目前常用的分离角膜内皮细胞的方法是从供体上撕除后弹力层和角膜内皮层,利用酶消化作用使角膜内皮细胞分离.常用的培养基为基础培养基加各种生长因子.这些生长因子在一定程度上促进细胞增殖,但培养的角膜内皮细胞长期传代后仍难以维持正常的细胞形态和功能.基因转染技术建立了永生化角膜内皮细胞系,有关细胞周期、信号通路和离子通道的研究成果也促进了角膜内皮细胞体外培养的研究进展.本文综述了角膜内皮细胞体外培养各个环节的最近进展.