新世纪治疗青光眼存在的问题及治疗模式转化

青光眼是一种引起视神经损害的疾病.视神经由很多神经纤维组成,当眼内压增高时,可导致神经纤维损害,引起视野缺损.早期轻微的视野缺损通常难以发现,如视神经严重受损,可导致失明.尽早地进行青光眼的检查、诊断和治疗是防止视神经损害和失明的关键.本文重点分析了现阶段青光眼治疗存在的问题及治疗模式的转变.     

CD4＋CD25＋Treg细胞对肿瘤免疫影响的研究进展

免疫系统可以保护机体遭受生物的侵袭,但也可以导致反应过度或错误反应,对自身正常组织发生攻击,从而引起自身免疫性疾病或攻击移植的组织器官,引发排斥反应,因此研究免疫耐受机制具有重大的理论意义和应用价值。早期研究认为免疫耐受机制主要包括自身反应性胸腺细胞及前B细胞在中枢免疫器官的克隆清除和免疫忽视两种机制。     

雌激素、孕激素与免疫调控关系的研究进展

雌激素、孕激素不仅参与生殖系统的生长发育，同时对机体免疫系统也有重要的调控作用。雌孕激素可以调节固有免疫和适应性免疫；雌孕激素含量和功能的失调可以导致自身免疫性疾病。目前，国内外学者通过大量的实验和临床研究，逐步揭示了雌孕激素在免疫调节中的作用，为研究某些发病机制不明的疾病提供了一定的理论依据。     

免疫相关因素在青光眼视神经损伤中的作用

青光眼是一种常见的获得性视神经疾病,青光眼视神经损伤是以视网膜神经节细胞凋亡为基本病理基础,但其具体机制尚不明了.有证据表明小胶质细胞及抗体和补体成分在青光眼的视神经损伤过程中扮演重要角色,对小胶质细胞及抗体和补体成分如何导致视网膜神经节细胞凋亡进行了解很有必要.     

原发性闭角型青光眼的治疗

原发性闭角型青光眼是我国青光眼的主要类型,也是致盲的主要原因之一。原发性闭角型青光眼由于治疗的不及时或治疗不当,随着病情的进展,可最终导致失明,其病因主要是由多种因素导致房角关闭使眼压升高,进而视神经受损所致。目前对于原发性闭角型青光眼的治疗多种多样,但由于引起房角关闭的因素多样化,导致我们在选择治疗方式上存在诸多困惑。为了原发性闭角型青光眼能尽早的给与恰当的治疗及预防,诸多学者和临床医师对原发性闭角型青光眼的发病机制和治疗做了大量研究,也对原发性闭角型青光眼的手术治疗方式做了许多改进,为原发性闭角型青光眼的治疗提供了新方法新思路。     

生命早期应激对成年后免疫功能的影响

灵长类动物在胎儿和新生儿阶段,其未成熟的免疫系统容易受损伤,许多流行病学和动物研究资料已报道生命早期应激对生命机体功能紊乱的重要影响作用。生命早期应激不仅引起啮齿类和灵长类动物HPA轴、脑神经递质和免疫系统的改变,还引起人类HPA轴、脑神经递质和免疫系统的的改变。研究生命早期应激引起成年后外周免疫功能的改变,揭示生命早期应激可能导致的相关免疫性疾病非常有意义。     

呵护你的“心灵之窗”

青光眼性视神经损害是全世界首要的致盲原因之一,它是一组以不可逆性视神经损伤为特征的疾病,眼压升高是其主要危险因素。随着医学模式的转变,眼科方面的心身问题也日益受到重视。原发性青光眼已被确认是一种典型的心身疾病,也就是说,青光眼的发生、发展及转归与社会心理因素密切相关。     

原发性开角型青光眼致病基因研究进展及研究策略

青光眼是一种以视神经损伤和相应视功能损害为特征的视神经疾病,具有渐进性、不可逆性和遗传异质性的特点,是位居第二的致盲性疾病,其中原发性开角型青光眼则最为常见.此文对青光眼经典的遗传学研究策略及主要的研究进展进行简要的概述;对采取全外显子组测序(whole-exome sequencing)鉴定致病基因的策略、面临的挑战及采取的对策进行系统的阐述.     

视神经三维结构可视化及定量测量

目的:定量分析眼底视神经的损伤用于青光眼的早期诊断。通过青光眼患者和正常对照组眼底视神经乳头可视化三维结构对比,研究青光眼患者眼球内部筛板、视神经束等框内视神经结构的定量形态学变化,分析青光眼下框内视神经损伤的定量评价。方法:采集正常对照组6例,青光眼组6例。利用光学相干断层成像获得青光眼组和对照组的视神经乳头的断层容积图像,采用三维可视化和多平面绘制对视神经乳头进行三维重建,并对可见筛板区域面积、可视筛孔数量、平均面积和总面积及可视视神经束的长度、宽度进行定量测量,并进行数据对比分析,用SPSS 19.0软件进行统计分析。结果:青光眼患者组和正常对照组在可视筛板面积、可视筛孔的面积及个数有明显差异,可视视神经束的长度及宽度无明显差异。结论:通过对青光眼患者的视神经乳头可视化结构的定量测定,获得青光眼视神经乳头部分结构的形态变化,青光眼患者筛板及筛板前组织明显变形,筛孔的可见面积和数量明显增加,视神经形态无明显差异。分析青光眼致病过程,有助于青光眼致病机理的研究,帮助获得青光眼早期诊断的依据和方法,具有一定的临床价值。     

小干扰RNA在类风湿性关节炎治疗的研究进展

类风湿性关节炎(RA)是一种慢性、对称性多关节炎,其伴有侵蚀性骨破坏及全身多系统受累。自身免疫系统紊乱被认为是RA发病的关键所在,相关易感基因的刺激等常会导致自身免疫系统紊乱,而自身免疫系统紊乱又会导致疾病的发生发展。RA的传统治疗主要包括免疫抑制剂和生物制剂。RNA干扰(RNAi)可干扰免疫因子使其表达沉默可以减少RA的炎症进展及缓解疾病发展。最近关于RNAi的效应分子小干扰RNA(siRNA)介导的基因沉默在自身免疫性疾病的治疗中取得了很大的进展,尤其是对RA的治疗作用。     

Estrogen deficiency accelerates aging of the optic nerve

The aim of this study was to provide a comprehensive review on hormone-based pathophysiology of aging of the optic nerve and glaucoma, including a literature review and expert opinions. Glaucoma, a group of intraocular pressure-related optic neuropathies, is characterized by the slow progressive neurodegeneration of retinal ganglion cells and their axons, resulting in irreversible visual sensitivity loss and blindness. Increasing evidence suggests that glaucoma represents the accelerated aging of the optic nerve and is a neurodegenerative disease of the central nervous system. This review highlights the high burden of glaucoma in older women and the importance of understanding the hormone-related pathophysiology of optic nerve aging and glaucoma in women. Strong epidemiological, clinical, and experimental evidence supports the proposed hypothesis that early loss of estrogen leads to premature aging and increased susceptibility of the optic nerve to glaucomatous damage. Future investigations into the hormone-related mechanisms of aging and glaucoma will support the development of novel sex-specific preventive and therapeutic strategies in glaucoma.     

Regional pathology in glaucoma – An overlooked link to neuroprotective strategies

Primary open-angle glaucoma (POAG) is the second commonest cause of blindness in the world. It is a neurodegenerative disease characterized by retinal ganglion cell loss. The molecular mechanism leading to glaucoma damage is unclear. Understanding the pathways that favor neuronal survival plus those that predispose to neuronal demise in POAG may have direct implications for other neurodegenerative diseases. POAG is a heterogeneous disease. A small subset of POAG patients develop damage in a highly focal form with a discrete sector of the optic nerve manifesting well delineated neuronal loss. It is hypothesized that this pattern of nerve loss indicates the optic nerve is not molecularly homogeneous. Genetic analysis of patients with isolated focal forms of POAG may enable new genes to be identified in glaucoma. Finding the responsible genes in POAG is a critical first step. The potential implications are earlier disease detection with resultant optimized visual preservation. Future treatment options could develop that include altered gene regulation, gene silencing or introducing repair genes. Determining the molecular causes for regional neuronal susceptibility could lead to identification of pathways underlying disease and ultimately effective patient-specific neuroprotective strategies.     

New insights into blindness; mechanical fatigue of optic nerve head in glaucomatous optic neuropathy

A common cause of blindness worldwide is glaucoma. It is characterized by visual field loss which is caused by optic nerve damage leading to glaucomatous optic neuropathy (GON). Modelling of GON development may be helpful for designing strategies to decelerate the rate of GON progression and prevent GON development at early stages. Attempts to complete the modelling of GON development continue. In this paper, it was speculated that the modelling could be more completed through a biomechanical point of view. GON may result from the mechanical fatigue effects of radial tensile stress (TS), caused by intra-ocular pressure (IOP), on the optic nerve head (ONH). The mechanical fatigue rate is influenced by patient’s age, the maximum and minimum magnitude of IOP, the amplitude of IOP and TS fluctuations, the ONH geometry, scleral thickness and biomechanical properties of the sclera, particularly the peripapillary part, and the axial length of the globe. Based on this model, more efficient strategies can be developed to augment the ONH and decelerate the progression of glaucomatous optic nerve damage, and even screen high-risk individuals at early stages.     

Neuroprotection in glaucoma

Currently, glaucoma is recognised as an optic neuropathy. Selective death of retinal ganglion cells (RGC) is the hallmark of glaucoma, which is also associated with structural changes in the optic nerve head. The process of RGC death is thought to be biphasic: a primary injury responsible for initiation of damage that is followed by a slower secondary degeneration related to noxious environment surrounding the degenerating cells. For example, retinal ishaemia may establish a cascade of changes that ultimately result in cell death: hypoxia leads to excitotoxic levels of glutamate, which cause a rise in intra-cellular calcium, which in turn, leads to neuronal death due to apoptosis or necrosis. Neuroprotection is a process that attempts to preserve the cells that were spared during the initial insult, but are still vulnerable to damage. Although not yet available, a neuroprotective agent would be of great use in arresting the progression of glaucoma. There is evidence that neuroprotection can be achieved both pharmacologically and immunologically. Pharmacological intervention aims at neutralising some of the effects of the nerve-derived toxic factors, thereby increasing the ability of the spared neurons to cope with stressful conditions. On the other hand, immunological interventions boost the body's own repair mechanisms for counteracting the toxic effects of various chemicals generated during the cascade. This review, based on a literature search using MEDLINE, focuses on diverse cellular events associated with glaucomatous neurodegeneration, and discusses some pharmacological agents believed to have a neuroprotective role in glaucoma.     

Assessing optic nerve pathology with diffusion MRI: from mouse to human

The optic nerve is often affected in patients with glaucoma and multiple sclerosis. Conventional MRI can detect nerve damage, but it does not accurately assess the underlying pathologies. Mean diffusivity and diffusion anisotropy indices derived from diffusion tensor imaging have been shown to be sensitive to a variety of central nervous system white matter pathologies. Despite being sensitive, the lack of specificity limits the ability of these measures to differentiate the underlying pathology. Directional (axial and radial) diffusivities, measuring water diffusion parallel and perpendicular to the axonal tracts, have been shown to be specific to axonal and myelin damage in mouse models of optic nerve injury, including retinal ischemia and experimental autoimmune encephalomyelitis. The progression of Wallerian degeneration has also been detected using directional diffusivities after retinal ischemia. However, translating these findings to human optic nerve is technically challenging. The current status of diffusion MRI of human optic nerve, including imaging sequences and protocols, is summarized herein. Despite the lack of a consensus among different groups on the optimal sequence or protocol, increased mean diffusivity and decreased diffusion anisotropy have been observed in injured optic nerve from patients with chronic optic neuritis. From different mouse models of optic nerve injuries to the emerging studies on patients with optic neuritis, directional diffusivities show great potential to be specific biomarkers for axonal and myelin injury.     

Are intracranial pressure fluctuations important in glaucoma?

Glaucoma is one of the leading causes of irreversible blindness. Primary open-angle glaucoma (POAG), the most common type, is a progressive optic neuropathy with characteristic structural changes in the optic nerve head and functional changes in the visual field. Mechanical and vascular theories for the pathogenesis of glaucomatous optic neuropathy have been proposed. Elevated intraocular pressure (IOP) is a strong risk factor, although a subset of POAG patients has normal IOP and is designated normal tension glaucoma (NTG). Clearly, factors other than IOP are likely to be involved in retinal ganglion cell death in glaucoma. An intriguing finding of recent studies is that intracranial pressure (ICP) is lower in patients with POAG and NTG when compared with nonglaucomatous control subjects. It has been suggested that the relationship between IOP and ICP may play a fundamental role in the development of glaucoma. A decreased ICP could result in an increased trans-lamina cribrosa pressure difference (IOP minus ICP) and lead to glaucomatous damage. In the present paper, we raise the question of whether ICP fluctuations also may be important in glaucoma. The effect of ICP fluctuation might be comparable to that of IOP fluctuation, which has been recognized as an independent risk factor for glaucoma progression.     

Minimum distance mapping using three-dimensional optical coherence tomography for glaucoma diagnosis

Objective imaging of the optic nerve structure has become central to the management of patients with glaucoma. There is an urgent need in diagnosis and staging for reliable objective precursors and markers. Three-dimensional ultrahigh-resolution frequency domain optical coherence tomography (3D UHR OCT) holds particular promise in this respect since it enables volumetric assessment of intraretinal layers including tomographic data for the retinal nerve fiber layer (RNFL) and optic nerve head. The integrated analysis of this information and the resolution advantage has enabled the development of more informative indices of axonal damage in glaucoma compared with measurements of RNFL thickness and cup-to-disc ratio provided by commercial OCT devices. The potential for UHR OCT in enabling the combined analysis of tomographic and volumetric data on retinal structure is explored. A novel parameter was developed; the three-dimensional minimal distance as the optical correlate of true retinal nerve fiber layer thickness around the optic nerve head region. For the purposes of this pilot study, we present data from a normal subject and from two patients with characteristic optic nerve and retinal nerve fiber layer changes secondary to glaucoma.     

Therapeutic potentials of aspirin in glaucomatous optic neuropathy

Glaucoma is a common blinding disease worldwide. Although traditionally considered as a disease of elevated intraocular pressure, it is now clear that glaucoma is primarily a distinctive optic neuropathy with many proposed pathogenic mechanisms. Impaired blood flow resulting in ischemia has been proposed to be involved in the retinal ganglion cell loss seen in glaucoma. Aspirin might improve optic nerve head perfusion by stabilizing microcirculatory flow. Evidence also indicates that apoptosis may be the final common pathway for ganglion cell death in glaucoma. Aspirin has been shown to exhibit neuroprotective properties. Prostaglandins play an important role in the regulation of intraocular pressure. Aspirin is well known to inhibit cyclooxygenase mediated prostaglandin synthesis. The NSAID-inhibition of PGs synthesis up-regulates the concentration prostaglandin receptors in retinovascular tissues. Based on the body of evidence implicating ocular blood flow disturbances, apoptotic cell death, and also the role of prostaglandins in the pathogenesis of glaucoma we hypothesize that aspirin could be potentially useful drugs in the treatment of glaucoma. Hypothetical pathophysiologic mechanisms explaining potential beneficial effects of aspirin on glaucomatous optic neuropathy include: increasing optic nerve blood flow, preventing retinal ganglion cell death through neuroprotective mechanisms, and upregulating prostaglandin receptors.     

Clinical approach to normal intraocular pressure glaucoma

Normal intraocular pressure (IOP) glaucoma is a clinical condition characterized by pathologic optic nerve excavation and visual field impairment, defined as optic neuropathy with certain features of a disease known as glaucoma. Glaucomatous optic nerve lesion is characterized by optic disk excavation or depression, however, this feature may greatly vary. The level of IOP is considered only one of the multiple risk factors involved in the disease development. In normal IOP glaucoma, papillary lesions and visual field impairments may differ from those occurring in primary open-angle glaucoma. In modern ophthalmology, the terminology has been modified, so the term low IOP glaucoma has been replaced by the term normal IOP glaucoma. It is now believed that various factors play a role in the development of glaucomatous optic neuropathy in normal IOP glaucoma and show variable interference depending on IOP level. Additional studies are needed to define these interactions and their impact on the mechanism of glaucomatous excavation. This will hopefully pave the way to new therapeutic approaches and help in clinical decisions concerning the prognosis and treatment of individual patients.