过氧化物酶体增生物激活受体γ在鼠眼球中的分布

背景过氧化物酶体增生物激活受体γ（PPAR-γ）是一类由配体激活的核转录因子,是潜在的抗炎、抗纤维增生、抗新生血管形成及神经保护因子,其在动物和人体组织中的生理病理功能是目前的研究热点之一,PPARγ与眼科疾病的研究受到关注。目的研究PPARγ在眼部不同组织细胞中的表达,为PPARγ激动剂在眼科疾病治疗中的应用提供参考依据。方法取SPF级C57BL／6J小鼠6只及SD大鼠1只,用质量分数3％水合氯醛麻醉处死后立即摘除眼球,采用Western blot法检测小鼠角膜、晶状体和视网膜组织中PPARγ蛋白的表达;采用免疫组织化学和免疫荧光化学法检测PPARγ在小鼠角膜、晶状体、视网膜、睫状体及视神经组织中的表达及定位。结果Western blot法检测表明,PPARγ在小鼠角膜、晶状体、视网膜中均呈阳性表达。免疫组织化学和免疫荧光化学法检测显示,PPARγ在角膜组织中主要表达于上皮层,以基底细胞染色最强,而角膜内皮及基质细胞上仅有弱表达。PPARγ在晶状体中主要表达于上皮细胞和浅皮质层;在视网膜组织中,PPARγ主要表达于视网膜节细胞层、内丛状层、外丛状层和内核层,此外PPARγ在SD大鼠睫状体组织中主要表达于无色素上皮。免疫荧光化学法检测显示,其在视网膜中与Muller细胞标志物谷氨酰胺合成酶（GS）共定位表达明显;PPARγ在视神经组织中的表达与星形胶质细胞标志物胶质纤维酸性蛋白（GFAP）共定位表达明显。结论PPARγ广泛分布于眼不同组织中并呈特异性表达,该结果为相关眼科疾病的靶向治疗提供了依据。     

趋化因子受体3在脉络膜新生血管性疾病中的研究进展

趋化因子受体3( CCR3)是一种新的趋化因子受体,在一些炎症免疫疾病中发挥重要作用.CCR3在眼部主要分布于视网膜色素上皮细胞中,亦可表达于脉络膜血管肉皮细胞中.在一些脉络膜新生血管(CNV)疾病发现CCR3表达;在CNV动物模型中CCR3活化能够促进新生血管形成.通过CCR3抗体和基因敲除方法抑制CCR3和其配体,能够使动物模型中CNV面积明显减小;使用CCR3拮抗剂亦能够显著抑制CNV的体积.进一步深入研究CCR3及其配体生理状态下在眼部的分布和表达,了解其在CNV疾病发生发展中的变化规律及机制,对于CNV形成研究以及寻找CNV形成的检测指标和新一代CNV治疗药物具有积极意义.     

趋化因子受体3及其配体在眼部疾病中的作用

趋化因子受体3 （CCR3）及其配体eotaxin是一种与哮喘和过敏相关的炎性因子,研究发现CCR3及其配体与多种眼科疾病相关,如脉络膜新生血管、变态反应性结膜炎、视网膜中央静脉阻塞、年龄相关性黄斑变性、视网膜变性等.CCR3的生物学功能研究认为,CCR3及其配体eotaxin不仅参与促进嗜酸性粒细胞与肥大细胞的运输,还参与炎症反应过程,了解其在眼部疾病发生及发展过程中的作用对于眼科相关疾病的认识和诊治有重要意义.就CCR3及其配体的结构和生物学功能以及其与一些眼部疾病的关系进行综述.     

肝脏X受体在眼科疾病中的研究进展

肝脏X受体（liver X receptors，LXR）是一种配体激活的核转录因子，属于核受体超家族成员。LXR不但参与脂类和胆固醇代谢的调节，还影响了多种炎症反应过程，因此其在脂类代谢异常和炎症相关疾病中的研究较多。近年发现，LXR在眼部疾病的发生发展中也发挥了重要作用。本文拟就LXR的结构、特征、参与眼部疾病的作用机制以及临床治疗前景进行综述。     

Ephrin配体和Eph受体酪氨酸激酶家族在眼部血管发生中的作用

在正常发育以及多种疾病过程中血管发生都发挥着重要作用,包括肿瘤血管发生、缺血性修复以及损伤愈合等.近年来,人们逐渐关注到Eph受体和其配体在血管形成以及血管发生中的作用.Eph受体家族是最大的受体酪氨酸激酶系统,Eph受体和它们的膜锚定配体Ephrin的特点是能够介导双向信号,传递位置导向信息,作用于发育中的血管系统细胞,控制动静脉非对称地建立,从而起着装配新生血管的作用.Ephrin/Eph系统在眼部血管发生相关疾病中的作用也越来越受到关注,目前已在角膜、视网膜以及脉络膜的新生血管上发现Ephrin/Eph系统具有作用.本文介绍Eph-fin配体和Eph受体酪氨酸激酶家族,综述其在眼部血管发生中的作用.     

G蛋白信号转导调节子5在眼科的应用进展

G蛋白信号转导调节子5(regulators of G-protein signaling 5,RGS5)是RGS家族重要成员之一,不仅负向调控G蛋白耦联受体相结合的信号转导,还能抑制下游的丝裂原激活蛋白激酶通路激活.其与缺氧及病理性新生血管形成密切相关.RGS5与眼部和其他组织疾病的关系及其作用机制有待进一步深入研究.     

三磷肌醇,环磷酸腺苷对视网膜色素上皮功能影响的研究进展

视网膜色素上皮（ｒｅｔｉｎａｌｐｉｇｍｅｎｔｅｐｉｔｈｅｌｉｕｍ，ＲＰＥ）胞膜上具有特异性受体，能辨认视细胞外节膜盘（ｒｏｄｏｕｔｅｒｓｅｇｍｅｎｔ，ＲＯＳ）上的特异性配体，受体与配体相互作用，ＲＰＥ细胞内三磷肌醇（ｉｎｏｓｉｔｏｌｔｒｉｐｈｏｓｐｈａｔｅ，ＩＰ３）的水平增高，可促使ＲＰＥ对ＲＯＳ的吞噬。另外，ＲＰＥ胞膜上的毒蕈碱受体与其激动剂作用后也可促使ＲＰＥ细胞内ＩＰ３的增高及对ＲＯＳ吞噬的增强。环磷酸腺苷（ｃｙｃｌｉｃａｄｅｎｙｌａｔｅｍｏｎｏｐｈｏｓｐｈａｔｅ，ｃＡＭＰ）则作用相反，ＲＰＥ细胞膜上存在β２肾上腺素能受体，其受体激动剂可刺激ＲＰＥ细胞内ｃＡＭＰ浓度的迅速升高，抑制ＲＰＥ的吞噬功能。ＩＰ３和ｃＡＭＰ之间是否有拮抗作用目前尚不清楚。ｃＡＭＰ还抑制ＲＰＥ细胞的趋化、迁移、和增殖，其机制不明。另外，ｃＡＭＰ通过促进ＲＰＥ胞膜上ＮＡ＋－Ｋ＋－ＡＴＰ酶的活性及抑制ＣＬ－由视网膜向脉络膜的转运而抑制视网膜下液的转运。     

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.     

免疫检查点抑制剂相关眼部毒性:全球文献病例统计分析

免疫检查点抑制剂通过抑制细胞毒性T淋巴细胞相关抗原-4、程序性死亡受体-1、程序性死亡配体-1阻断肿瘤的免疫逃逸途径,从而达到杀伤肿瘤细胞的目的.然而,免疫系统的激活也会引起免疫相关的不良反应.尽管免疫检查点抑制剂所导致的眼部毒性并不常见,但是能够涉及到眼部所有组织,可能影响部分患者的免疫检查点抑制剂的使用疗程.本文通...     

新型C型凝集素受体mincle的研究进展

巨噬细胞诱导型C型凝集素受体mincle是一种新发现的非经典型C型凝集素受体,主要表达于抗原递呈细胞表面,可以在某些真菌、结核分枝杆菌、坏死细胞的刺激下与相关配体结合,激活核因子-κB(NF-κB)途径,引起炎性因子的表达,从而在宿主的固有免疫应答过程中发挥一定的作用.目前,mincle受体在一些免疫相关疾病中作用机制的研究成为热点,但关于其在眼科炎性感染性疾病中作用的研究甚少,深入研究mincle受体与眼科感染性疾病的关系可以为相关疾病的免疫治疗提供新的思路.就mincle受体的基本概念、作用机制、与炎性疾病的关系以及其在眼科疾病研究中的展望进行综述.     

Rho/ROCK信号通路在眼科疾病发生发展中的作用研究进展

眼科疾病的发生发展与细胞生理功能和眼组织功能异常密切相关,其中相关信号通路的调控发挥了重要作用。Rho/ROCK信号通路可参与多种细胞事件,包括诱导细胞骨架重组、细胞黏附、细胞增殖和血管生成,并可在细胞周期进展、细胞分化和细胞凋亡中发挥显著作用。研究表明,Rho/ROCK信号通路在眼组织中分布广泛,其异常活化可影响眼组织的正常生理功能,与眼病的发生发展关系紧密。本文对Rho/ROCK信号通路在眼科疾病发生发展中的作用简要综述,为临床治疗眼病提供思路。     

The control of conjunctival fibrosis as a paradigm for the prevention of ocular fibrosis-related blindness. “Fibrosis has many friends”

The processes involved in ocular fibrosis after disease or ocular tissue injury, including surgery play an important part in the development or failure of treatment of most blinding diseases. Ocular fibrosis is one of the biggest areas of unmet need in ophthalmology. Effective anti-scarring therapies could potentially revolutionise the management of many diseases like glaucoma worldwide. The response of a quiescent or activated conjunctiva to glaucoma surgery and aqueous flow with different stimulatory components and the response to different interventions and future therapeutics is a paradigm for scarring prevention in other parts of the eye and orbit. Evolution in our understanding of molecular and cellular mechanisms in ocular fibrosis is leading to the introduction of new and re-purposed therapeutic agents, targeting a wide range of key processes. This review provides current and futures perspectives on different approaches to conjunctival fibrosis following glaucoma surgery and highlights the challenges faced in implementing these therapies with maximal effect and minimal side effects.Subject terms: Inflammation, Conjunctival diseases     

TGF-BETA信号通路介导的眼组织纤维化在眼病发生发展中作用的研究进展

眼科疾病的发生发展与眼组织的异常发育和功能障碍有关,其中相关信号通路的异常活化可使眼组织纤维化进而使其生理功能发生障碍,在眼病的发生和发展过程中发挥重要作用。转化生长因子β(TGF-β)信号通路广泛存在于各类细胞中,可参与细胞的生长、增殖和分化调节,是介导组织发生纤维化的关键信号通路。有研究发现,TGF-β信号通路可在青光眼、眼眶纤维化、增生性玻璃体视网膜病变等眼病中发挥作用。本文就TGF-β信号通路介导的眼组织纤维化在眼病发生发展中的作用研究进展进行简要综述。     

程序性死亡分子-1及其配体通路在眼科领域的研究进展

共刺激信号已经成为免疫学研究的一个热点。程序性死亡分子-1（PD-1）及其配体属于抑制性共刺激分子,其在自身免疫性疾病、器官移植排斥反应、病原微生物感染、肿瘤免疫逃逸等方面都发挥着重要作用。近年来,PD—1及其配体（PD-1／PD—L）通路在眼科方面的研究也取得了一定进展。眼部多种疾病和现象,如眼部免疫性疾病、眼部感染性疾病、眼部肿瘤、眼组织的免疫赦免等均发现有PD—1／PD—L通路的改变。这些发现不仅进一步阐明了一些眼部疾病的发病机制,而且为其预防和治疗提供了新的方向。就PD—1／PD—L通路的生物学特性及其在眼科生理病理中的研究进展进行综述。     

Aging and ocular tissue stiffness in glaucoma

Glaucoma is a progressive and chronic neurodegenerative disorder characterized by damage to the inner layers of the retina and deformation of the optic nerve head. The degeneration of retinal ganglion cells and their axons results in an irreversible loss of vision and is correlated with increasing age. Extracellular matrix changes related to natural aging generate a stiffer extracellular environment throughout the body. Altered age-associated ocular tissue stiffening plays a major role in a significant number of ophthalmic pathologies. In glaucoma, both the trabecular meshwork and the optic nerve head undergo extensive extracellular matrix remodeling, characterized by fibrotic changes associated with cellular and molecular events (including myofibroblast activation) that drive further tissue fibrosis and stiffening. Here, we review the literature concerning the role of age-related ocular stiffening in the trabecular meshwork, lamina cribrosa, sclera, cornea, retina, and Bruch membrane/choroid and discuss their potential role in glaucoma progression. Because both trabecular meshwork and lamina cribrosa cells are mechanosensitive, we then describe molecular mechanisms underlying tissue stiffening and cell mechanotransduction and how these cellular activities can drive further fibrotic changes within ocular tissues. An improved understanding of the interplay between age-related tissue stiffening and biological responses in the trabecular meshwork and optic nerve head could potentially lead to novel therapeutic strategies for glaucoma treatment.     

P2Y2受体激动剂用于干眼治疗的研究进展

干眼属常见的眼表疾病,是指由于泪液的量和（或）质的异常引起的泪膜不稳定和眼表面的损害,从而导致眼部不适症状的一类疾病。目前我国干眼的治疗包括病因治疗、人工泪液替代治疗、抗炎治疗、免疫抑制剂治疗、手术治疗以及中医治疗等。Ｐ２Ｙ２受体激动剂是一种治疗干眼的新型药物,它能够通过激动位于眼表的Ｐ２Ｙ２受体,促使结膜上皮细胞泪液的分泌以及结膜杯状细胞对黏蛋白的分泌,从而增强泪膜稳定性,改善干眼症状。３０ｇ·Ｌ－１地夸磷索四钠滴眼液是目前唯一上市的Ｐ２Ｙ２受体激动剂。本文就近年来地夸磷索四钠用于干眼治疗的临床疗效、安全性以及相关研究进展作一综述。     

Circadian rhythms in the eye: the physiological significance of melatonin receptors in ocular tissues

Many biological processes display circadian rhythms in activity, which presumably operate to coordinate cellular functions with daily environmental oscillations. The diurnal changes in environmental illumination are conveyed by the retina to the brain to entrain circadian rhythms throughout the body. Many ocular tissues themselves exhibit circadian rhythms of activity to optimize specific processes which require coordination with the light-dark cycle. The circadian signaling molecule, melatonin, is secreted into the circulation from the pineal gland, and is also produced within specific ocular cells such as retinal photoreceptors, ciliary epithelial cells, and perhaps cells of the lens. Melatonin appears to entrain many aspects of the biological clock via activation of specific G-protein-coupled integral membrane melatonin receptors. Melatonin receptors have been identified in many ocular tissues, including the neural retina, retinal pigment epithelium, ciliary body, cornea, sclera, and lens. This review will describe the circadian rhythmicity of some of the functions of these various ocular tissues, and will attempt to correlate these circadian activities with the expression of specific G-protein-coupled melatonin receptors, the role of melatonin in the regulation of circadian activity in ocular tissues, and its potential role in ocular diseases.     

The hydrolysis of the prostaglandin analog prodrug bimatoprost to 17-phenyl-trinor PGF2alpha by human and rabbit ocular tissue.

Bimatoprost (Lumigan), the ethyl amide derivative of the potent prostaglandin FP agonist 17-phenyl-trinor PGF(2alpha), has been reported to be a member of a pharmacologically unique class of ocular hypotensive agents. To confirm that bimatoprost, which is intrinsically active as an FP prostaglandin agonist, is also a prostaglandin analog prodrug, the hydrolysis of bimatoprost by ocular tissues was studied by incubating solutions containing bimatoprost with either human or rabbit ocular tissue. The ethyl amide group of bimatoprost was hydrolyzed by rabbit and human cornea, iris/ciliary body and Thasclera to produce the expected carboxylic acid product, 17-phenyl-trinor PGF(2alpha). The rate of hydrolysis by human and rabbit cornea and iris/ciliary body is similar, whereas the rate of hydrolysis by the sclera is slower in humans than in rabbits. These studies show that human and rabbit ocular tissue (cornea, iris/ciliary body and sclera) can convert bimatoprost to the potent prostaglandin FP agonist 17-phenyl-trinor PGF(2alpha). Separate in vitro studies clearly show that both bimatoprost and 17-phenyl-trinor PGF(2alpha) have affinity for and are agonists at the human FP receptor. Taken together, the data strongly suggests that the ocular hypotensive effect of bimatoprost can be attributed to its activity as a prostaglandin receptor agonist either directly or through its role as a prostaglandin agonist prodrug.     

Modulating the tachykinin: Role of substance P and neurokinin receptor expression in ocular surface disorders

Substance P (SP) is a tachykinin expressed by various cells in the nervous and immune systems. SP is predominantly released by neurons and exerts its biological and immunological effects through the neurokinin receptors, primarily the neurokinin-1 receptor (NK1R). SP is essential for maintaining ocular surface homeostasis, and its reduced levels in disorders like diabetic neuropathy disrupt the corneal tissue. It also plays an essential role in promoting corneal wound healing by promoting the migration of keratocytes. In this review, we briefly discuss the structure, expression, and function of SP and its principal receptor NK1R. In addition, SP induces pro-inflammatory effects through autocrine or paracrine action on the immune cells in various ocular surface pathologies, including dry eye disease, herpes simplex virus keratitis, and Pseudomonas keratitis. We provide an in-depth review of the pathogenic role of SP in various ocular surface diseases and several new approaches developed to counter the immune-mediated effects of SP either through modulating its production or blocking its target receptor.