Toll样受体与眼部炎性疾病

Toll样受体是一类存在于哺乳动物细胞的跨膜受体,它可以识别病原微生物保守的病原相关分子模式,参与细胞信号传导及免疫反应,在抗感染中发挥重要作用.本文就Toll样受体家族成员的结构特点、其识别病原微生物参与信号传导及宿主免疫的功能及其与眼部疾病的联系进行综述,为深入研究眼部感染性及免疫性疾病的发病机制提供帮助,为这些疾病的治疗提供新的思路和手段.     

Toll样受体介导的信号通路及其与眼部感染性疾病的关系

Toll样受体(Toll-like receptors,TLRs)是一天然模板识别受体家族,能识别固有性模板,其介导的信号转导通路在对抗外来病原体的天然免疫应答中起重要作用。越来越多的研究已经发现人眼角膜细胞、巩膜、结膜、葡萄膜、视网膜、虹膜内皮细胞、睫状体等都能表达TLRs,而且与眼部的免疫和炎症反应密切相关。我们就TLRs的信号转导方式及其和眼部感染性疾病关系做一综述。     

Toll样受体在眼科的研究现状

Toll样受体是自身免疫的关键受体，它参与宿主对致病微生物的识别和防御等感染免疫过程，也与人体的获得性免疫密切相关，是目前免疫学研究的重点和热点。眼球作为感染性和免疫性疾病的好发部位，在感染免疫和获得性免疫方面与全身摹他器官有相似之处，但是其独特的解剖特点，例如血房水屏障、血视网膜屏障、角膜的无血管化等，使其免疫学特点的特异性也非常明显。就Toll样受体的特点以及在眼科的研究现状进行综述。     

Toll样受体介导的信号通路与感染性角膜病

Toll样受体（TLR）是一类跨膜受体，最初在果蝇体内发现，至今已在哺乳动物和人类细胞上发现11种TLR，分别识别细菌、病毒、真菌等致病微生物的病原相关分子结构，并经过下游信号转导通路启动先天免疫，可能也在自身免疫性疾病的发生中发挥重要作用。已经报告角膜上皮细胞表达功能性的TLR4和TLR5，分别识别绿脓杆菌的脂多糖和鞭毛蛋白。了解TLR信号转导通路将为感染性角膜病的治疗提供很多特异性的新靶点。     

Toll样受体在干眼发病机制中的研究进展

最近研究显示眼表引发免疫炎症反应的部分原因是眼表存在一类称为Toll样受体（TLRs）的蛋白家族。TLRs在眼部的表达受到感染和各种炎症环境的影响,例如单疱病毒、细菌、真菌性角膜炎,变态反应性结膜炎和干眼综合征。TLRs信号通路对抗原递呈细胞和T细胞介导的免疫炎症反应的激活起重要作用。近些年随着眼科学的发展,对TLRs在干眼发病机制方面的研究逐渐增多,现就TLRs的结构与配体,TLRs的信号转导路径,TLRs在眼表中的表达位置及表达模式,以及与干眼的相关性作一综述。     

NOD样受体与眼部炎性疾病的相关研究进展

NOD样受体是一类存在于哺乳动物中的胞内受体,可以识别病原微生物保守的病原相关分子模式,参与细胞信号传导及炎症小体的形成,并可以对其他免疫因子进行调控,在免疫反应中发挥重要作用.此文就NOD样受体家族成员的结构特点、免疫功能及其与眼部疾病的联系进行综述,力图为深入研究眼部感染性及免疫性疾病的发病机制提供帮助,为这些疾病的诊治提供新的思路和手段.     

Toll样受体信号通路和糖尿病视网膜病变的关系

糖尿病视网膜病变(diabetic retinopathy,DR)是导致失明的主要疾病之一,其发病机制尚未完全阐明.Toll样受体(Toll-like recetors,TLRs)是机体免疫系统识别、感知细菌、病毒等病原体入侵的重要分子,在机体免疫防御功能中发挥着重要作用.众多的研究提示糖尿病发病与免疫系统的激活密切相关,TLRs的激活在DR的发生发展中起着重要的作用.现就Toll样受体信号通路与糖尿病视网膜病变的关系作一综述,为DR的防治提供新的治疗手段和思路.     

Toll样受体介导的信号通路与感染性角膜病

Toll样受体(TLR)是一类跨膜受体,最初在果蝇体内发现,至今已在哺乳动物和人类细胞上发现11种TLR,分别识别细菌、病毒、真菌等致病微生物的病原相关分子结构,并经过下游信号转导通路启动先天免疫,可能也在自身免疫性疾病的发生中发挥重要作用。已经报告角膜上皮细胞表达功能性的TLR4和TLR5,分别识别绿脓杆菌的脂多糖和鞭毛蛋白。了解TLR信号转导通路将为感染性角膜病的治疗提供很多特异性的新靶点。     

脂多糖受体复合体在急性前葡萄膜炎虹膜色素上皮细胞中作用的研究进展

近年来,有研究结果表明人葡萄膜中的虹膜色素上皮细胞具有对脂多糖(LPS)反应的固有模式识别受体,包括Toll样受体(TLR)4、髓样分化蛋白(MD)2及分化簇(CD)14。这一发现扩展了微生物触发因子和葡萄膜固有免疫在急性前葡萄膜炎发病机制中的解释。提示LPS受体复合物成分可能成为该病的治疗靶点。本文中笔者对LPS受体复合体在人虹膜色素上皮细胞和葡萄膜炎动物模型中的研究现状进行综述。     

抗真菌免疫与角膜真菌感染

宿主与真菌之间的粘附是宿主抗真菌免疫的起始,随后通过Toll样受体对真菌的识别及信号传导,启动非特异性和特异性免疫应答。免疫反应在抗角膜真菌感染中发挥重要作用,但其机制仍不清楚。本文就抗全身及角膜真菌感染的免疫过程和机制研究进展作一综述,以期为研究真菌性角膜炎发病机制及抗角膜真菌感染提供借鉴。     

Toll-like receptors in ocular immunity and the immunopathogenesis of inflammatory eye disease

Microbial agents have an important role in the pathogenesis of various inflammatory eye diseases, such as uveitis and keratitis. Microbial infections of the eye such as microbial keratitis, ocular onchocerciasis, bacterial endophthalmitis, viral retinitis, and other infectious uveitis are unfortunately common. In addition, microbial agents have been implicated in the pathogenesis of "non-infectious" immune mediated diseases such as HLA-B27 associated acute anterior uveitis. Toll-like receptors (TLR) are a family of pattern recognition receptors that initiates rapid host innate immune response to microbial components known as pathogen associated molecular patterns, which are unique to a given class of microbes, such as lipopolysaccharide of Gram negative bacteria. Recent in vitro and in vivo studies have demonstrated the expression and function of TLRs in the eye, with significant implications for better understanding of ocular immunity and the pathogenesis of inflammatory eye diseases affecting the cornea, uvea, and retina.     

TLRs信号通路在干眼发病机制中的研究进展

Toll样受体(toll-like receptors,TLRs)是连接先天性免疫与获得性免疫的桥梁。随着对干眼发病机制研究的不断深入,TLRs及信号通路在干眼免疫应答中的诱导和调控作用日益受到关注。目前的研究表明,对TLRs及信号通路的调控有助于减轻或阻止干眼炎症反应过程,因此对TLR信号通路的调节及控制在干眼的治疗及预防中有重要的意义。本文总结TLRs及其信号通路参与干眼发病机制,不同干预方法对干眼TLR通路的影响,并对未来发展的前景及问题进行探讨。     

The role of chemokines and their receptors in ocular disease

The migration and infiltration of cells into the eye whether blood-borne leucocytes, endothelial or epithelial cells occurs in many ocular diseases. Dysregulation of this process is apparent in chronic inflammation, corneal graft rejection, allergic eye disease and other sight-threatening conditions. Under normal and inflammatory conditions, chemokines and their receptors are important contributors to cell migration. To date, 47 chemokines and 19 chemokine receptors have been identified and characterised. In recent years, investigations into the role of chemokines and their receptors in ocular disease have generated an increasing number of publications. In the eye, the best understood action of these molecules has arisen from the study of their ability to control the infiltration of leucocytes in uveitis. However, the involvement of chemokines in angiogenesis in several ocular conditions and in the survival of corneal transplants demonstrates the multifaceted nature of their effects. Interestingly, the constitutive expression of chemokines and their receptors in ocular tissues suggests that certain chemokines have a homeostatic function. In this review, we discuss the nature and function of chemokines in health and disease, and describe the role of chemokines in the pathogenesis of different ocular conditions.     

Recent advances in Toll‐like receptors and anterior uveitis

Uveitis involves acute, recurrent or chronic inflammation of the uvea, and occurs when the normal state of ocular immune privilege has broken down. Accumulating evidence implicates the role of microbial triggers in the development of various forms of immune‐mediated uveitis in addition to its causative role in infectious uveitis. Toll‐like receptors (TLRs) are the most important pattern‐recognition receptors of the innate immune system that recognize pathogen‐associated molecular patterns of microbes. Activation of TLRs by pathogen‐associated molecular patterns leads to the induction of an inflammatory cascade and activation of both innate and adaptive arms of the immune response. TLRs have been implicated in the pathogenesis of various inflammatory diseases, including uveitis. This review provides an update on recent progress in TLR research and uveitis, specifically summarizing new evidence for the role of TLRs in anterior uveitis. There have been important observations from studies involving human ocular tissue, clinical uveitis and from experimental animal models of uveitis, such as endotoxin‐induced uveitis. The ‘Toll rush’ has certainly gained momentum, and future advances in this field have the potential for selectively targeting the TLR pathway and ultimately translating into better therapies for patients with sight‐threatening uveitis.     

Toll-like receptors in ocular surface disease

The ability of the ocular surface to mount an immune response is in part attributed to a family of proteins called toll-like receptors (TLRs). The latter are evolutionary conserved receptors that recognize and respond to various microbes and endogenous ligands. In addition to their recognition function, TLR activation triggers a complex signal transduction cascade that induces the production of inflammatory cytokines and co-stimulatory molecules, thus initiating innate and adaptive immunity. Toll-like receptor expression at the ocular surface is modulated during infection (e.g. Herpes simplex, bacterial keratitis and fungal keratitis) as well as during various inflammatory conditions (allergic conjunctivitis and dry-eye syndrome). Here recent findings regarding TLR expression and their involvement in various ocular surface diseases are discussed.     

Dinucleoside polyphosphates in the eye: from physiology to therapeutics

Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological, pharmacological and therapeutic properties in the eye and other tissues. These compounds are formed by two adenosine moieties linked by their ribose 5′-ends to a variable number of phosphates. Diadenosine polyphosphates are present as active components of ocular secretions such as tears and aqueous humour and they can activate P2 purinergic receptors present on the ocular surface, anterior segment and retina. Both metabotropic and ionotropic actions mediated by P2Y and P2X receptors, respectively are responsible for the control of processes such as induction of tear secretion, lysozyme production or acceleration of corneal wound healing. Inside the eye the dinucleotide Ap₄A can reduce intraocular pressure by acting on P2Y₁ receptors present in trabecular meshwork cells and on P2X₂ receptors present on the cholinergic terminals located in the ciliary muscle. In the retina, derivatives of diadenosine polyphosphates can improve the re-absorption of fluids in retinal detachment. Altogether, diadenosine polyphosphates are not only dinucleotides with roles in the physiology of the eye but it is also possible that their properties may serve to help in the treatment of some ocular pathologies.