视网膜神经节细胞氧化应激损伤的药物治疗研究进展

氧化应激是机体内氧自由基的产生与清除的稳态失衡，导致细胞和组织的氧化损伤。氧化应激损伤在青光眼、缺血性视神经病变等眼科疾病中发挥着重要的作用，活性氧可以通过氧化应激损伤导致视网膜神经节细胞(RGCs)凋亡、坏死，进而引起不可逆的视功能损害。因此，抗氧化药物在治疗RGCs氧化损伤等致盲眼病中显示出潜在的优势。本文综述了RGCs氧化应激损伤的机制，归纳了化学合成药物和天然药物防治RGCs氧化损伤的研究进展，以期为RGCs氧化损伤相关疾病的治疗提供更好的参考。     

Nrf2/Keap1/ARE信号通路与眼科疾病

氧化应激与多种眼科疾病的病理过程相关。近年的实验研究发现抗氧化应激药物对多种眼球细胞具有良好的保护作用。转录因子核因子-Ｅ２相关因子２是细胞抗氧化反应的中枢调节者,在细胞的防御保护中发挥重要作用。本文就核因子-Ｅ２相关因子２信号通路与眼科疾病的关系进行综述。     

NF-κB在眼科领域的研究进展

核转录因子κB(nuclear factor-kappa B,NF-κB)是一种几乎存在于所有细胞中具有多向、多效调控作用的核转录因子。它可参与调控细胞的增生、分化、黏附、凋亡、炎症反应和免疫应答等生理病理过程,在机体的生长发育、炎症反应、免疫应答和肿瘤生长等方面发挥重要的作用。近些年的研究表明,NF-κB在眼科相关疾病的发病机制中占有重要的地位,尤其是眼表疾病、白内障、青光眼、葡萄膜炎、眼底疾病等,针对NF-κB活化的抑制可能成为眼科疾病治疗的新型靶点。本文将对NF-κB在眼科领域的研究报道进行综述。     

维生素D缺乏和DNA甲基化在年龄相关性黄斑变性中的研究现状

年龄相关性黄斑变性( age-related macular degeneration,
　　AMD)是世界范围内中老年人视力丧失的主要疾病之一,是多病因多因素多机制介导的慢性退行性眼科疾病。AMD确切发病机制仍不明确,众多研究发现年龄、遗传、营养失衡、表观遗传学、氧化应激、补体激活和炎症反应等多种因素参与其发病。近年来研究发现机体维生素D水平和DNA甲基化与AMD发病有一定关系。以下将维生素D缺乏和DNA甲基化在AMD发病机制的作用进行简要综述。     

补体激活与自噬在年龄相关性黄斑变性中的研究进展

年龄相关性黄斑变性(age-related macular degeneration,ARMD)是一种随年龄增长而发病率逐渐上升的黄斑部疾病,目前认为其发病因素与患者的年龄、遗传、吸烟、氧化应激、免疫炎症反应、RPE细胞老化和代谢异常等有关。补体系统在机体防御感染、免疫调节和炎症应答中扮演重要角色,补体系统异常激活引起免疫炎症近年来被认为是ARMD发病的重要原因。而自噬过程也参与了ARMD的发病。正常的自噬是细胞自我保护以及维持稳态的一个重要途径,当自噬被阻断时,可加剧氧化应激损伤,导致ARMD的发展。补体激活与自噬过程的均衡调节是控制ARMD发展的重要手段。     

TGF-β在增殖性视网膜疾病中的研究进展

转化生长因子-β(TGF-β)是一类具有多重功效的生物因子,参与调控细胞增殖、凋亡、分化,调节机体的免疫功能、炎性反应等。TGF-β信号通路介导的肌成纤维细胞转化与细胞外基质(ECM)过量积累导致视网膜组织收缩和功能受损。各种细胞因子信号参与视网膜组织中的纤维化反应,但TGF-β是影响视网膜纤维化疾病发病最关键的因子。就眼睛而言,角膜混浊、黄斑下纤维化和增殖性视网膜疾病等病理性纤维性疾病导致全世界数以百万计的人视力受损和失明,这仍然是眼科临床需求未得到满足的主要领域之一。故本文主要阐述TGF-β在增殖性视网膜疾病中的发病机制及治疗前景的相关研究进展,以期能为增殖性视网膜疾病的防治提供更多的分子靶点,为新药的研究提供新思路。     

DNA甲基化在眼科疾病中的研究进展

DNA甲基化作为表观遗传修饰的重要形式,通过调控基因表达,在疾病发生发展中发挥重要作用。近年来,随着DNA甲基化研究的迅速开展、检测技术的不断提升,DNA甲基化修饰已成为探究疾病发病机制及探寻新的治疗方案的重要方法; 眼科不同亚专业疾病在DNA甲基化的基础研究方面也取得了很多突破,包括角膜上皮的修复、结膜上皮的细胞黏附与异常的基质重塑、眼组织纤维化与青光眼、氧化应激和炎症反应与细胞损伤、不同DNA甲基化水平与眼部肿瘤的关系等。本文旨在通过对不同眼科疾病DNA甲基化调控机制的相关研究进行概述,为眼病发病机制的研究、筛查、诊断及预防提供新思路。     

年龄相关性黄斑变性与氧化应激相关性研究进展

年龄相关性黄斑变性(age-related macular degeneration,ARMD)是发达国家老年人致盲的首要疾病.ARMD是一种多因素疾病,其发病受遗传、环境、饮食、炎症反应及氧化应激等多种因素的影响,其中氧化应激在ARMD的发生、发展中起重要作用.近年研究发现氧化应激与ARMD的发病明显相关.这篇综述概括总结了ARMD的病理学特点、氧化应激与视网膜的关系以及氧化应激在ARMD形成过程中的研究进展.     

B7:CD28/CTLA-4共刺激分子及其在眼科的研究进展

大量实验证实B7家族分子与其受体CD2 8和CTLA 4结合后所产生的共刺激信号在T淋巴细胞激活中起重要作用 ,决定着受到抗原刺激的T细胞是分化、增殖为效应细胞 ,还是进入无反应状态。其在眼科的研究主要集中于眼科自身免疫性疾病、角膜和视网膜三个方面 ,阻断B7:CD2 8/CTLA 4通路可能为眼科自身免疫性疾病、角膜移植排斥反应和视网膜葡萄膜疾病的治疗提供新的途径。本文就其分子特性、功能及其在眼科的研究进展等方面的有关资料作一综述。     

视网膜色素上皮细胞的损伤因素与治疗进展

视网膜色素上皮（RPE）细胞在维持视网膜和脉络膜的正常功能和组织结构方面发挥重要作用，许多因素可导致RPE细胞的损伤，如缺氧、物理因素、化学物质和药物、免疫因素、氧化应激等。RPE细胞的损伤可导致多种眼底疾病，引起视功能的损害或丧失。深入研究引起RPE细胞损伤的因素对各种RPE细胞相关性眼病的预防和治疗具有十分重要的意义。近年来相关的研究日益受到关注，对RPE细胞损伤的影响因素及治疗方法进行综述。     

The potential value of natural antioxidative treatment in glaucoma

Glaucomatous optic neuropathy implies loss of retinal ganglion cells, including their axons, and a major tissue remodeling, especially in the optic nerve head. Although increased intraocular pressure is a major risk factor for glaucomatous optic neuropathy, there is little doubt that other factors such as ocular blood flow play a role as well. Mechanisms leading to glaucomatous optic neuropathy are not yet clearly understood. There is, however, increasing evidence that both an activation of glial cells and an oxidative stress in the axons play an important role. Glial cells may be activated by mechanical stress via activation of the epidermal growth-factor-receptor, or by ischemic stress via an increase in endothelin. Several factors can systemically or locally increase oxidative stress. In glaucoma, an unstable ocular blood flow leading to repeated mild reperfusion seems to be most relevant in inducing oxidative stress. The simultaneous production of nitric oxide in the astrocytes and of superoxide in the mitochondria of the axons leads to the production of the damaging peroxynitrite. Therapeutically, we need to reduce intraocular pressure, stabilize ocular blood flow, and reduce oxidative stress. Various natural compounds possess potential antioxidative value. Reduction of oxidative stress at the level of mitochondria can be achieved by gingko biloba. Polyphenolic compounds, such as tea, red wine, dark chocolate, or coffee have antioxidative properties. Coffee contains 3-methyl-1,2-cyclopentanedione (MCP), capable of scavenging peroxynitirite. Red wine-polyphenols (e.g., resveratrol), exert vasoprotective effects by inhibiting the synthesis of endothelin-1. Dark chocolate decreases blood pressure and improves endothelium-dependant vasorelaxation. Anthocyanosides (bilberries) owe their antioxidant effects to their particular chemical structure. Other antioxidants include ubiquinone and melatonin.     

氧化应激因素在干眼中的实验研究

干眼是指任何原因造成的泪液质或量异常或动力学异常,导致泪膜稳定性下降,并伴有眼部不适和(或)眼表组织病变特征的多种疾病的总称。干眼是一种多因素疾病,受年龄、环境因素影响较大。其中氧化应激因素与年龄相关性干眼关系密切。本文将基于动物实验研究,通过建立氧化应激实验动物模型,并监测眼表组织氧化损伤的生物标志物及抗氧化防御物水平,指出氧化应激在干眼中的作用。另外,一些介入性实验研究表明,氧化应激可能是干眼局部治疗的直接靶点。某些物质可以有效降低氧化应激损伤,从而达到治疗干眼的效果。近年来对氧化应激的进一步研究发现其在干眼中具有越来越重要的作用,为针对氧化应激的临床干预提供了依据。     

High-fat diet induces dry eye-like ocular surface damages in murine

PurposeA high-fat diet leads to dysfunction in multiple systems of the body. Herein we investigate the effects of a high-fat diet on the ocular surface using a murine model.MethodsFour-week-old male C57BL/6 mice were fed with a standard-fat diet (10 kcal% fat, SFD) or a high-fat diet (60 kcal% fat, HFD) for 1 or 3 months. Phenol red thread test was used to detect tear production, oregon green dextran (OGD) staining was performed to assess corneal epithelial permeability, and PAS staining was conducted to ascertain the presence of conjunctival goblet cells. Squamous metaplasia in the ocular surface and corneal epithelial barrier function were detected by immunofluorescent staining, zymography and Western blot analysis. Oxidative stress related protein expression was evaluated by immunostaining and Western blot analysis. Corneal and conjunctival cell apoptosis was determined by TUNEL assay and caspase-3 expression.ResultsA HFD induced obvious ocular surface damages, including decreased tear production, notable OGD staining and distinct goblet cell loss. It also resulted in corneal epithelial barrier dysfunction and significant squamous metaplasia of the corneal and conjunctival epithelia. The HFD also upregulated key factors that regulate oxidative stress in the ocular surface, and upregulated cell apoptosis in ocular surface epithelial cells.ConclusionsA HFD induces dry eye-like ocular surface damages in mice via the activation of oxidative stress and an induction of apoptosis in the cells of the ocular surface.     

Association between endoplasmic reticulum stress and risk factors of diabetic retinopathy

Diabetic retinopathy (DR) is one of the most common and challenging ocular complications of diabetes mellitus. As a chronic, progressive ocular disease that poses a serious threat to vision, DR has gradually become a leading cause of blindness worldwide. Emerging evidence points to an important role of endoplasmic reticulum (ER) stress in not only maintaining the steady-state equilibrium in the body, but also in intracellular synthesis, protein folding, and other essential functions. Recent studies have demonstrated clear associations between ER stress-related physiological functions and the pathogenesis of DR. When cells are stimulated by external stimuli, UPR pathway is activated firstly to protect it. However, long-term harmful factors can induce ER stress. which interferes with the physiological metabolism of retinal cells and participates in the occurrence of DR via the ATF6 pathway, PERK pathway and IRE1 pathway. At present, ER stress blocker is expected to become a new anti-DR therapy. Thus, understanding the relationship between ER stress and DR will help to develop new effective preventative treatments. In this review, we summarize the risk factors of DR pathogenesis induced by ER stress toward revealing potentially new therapeutic targets.     

获得性免疫在干眼的启动与维持

干眼(dry eye,DE)是一种由多种因素介导,发病机制复杂的常见慢性眼表疾病。干眼致病因素主要包括免疫炎症,氧化应激,泪膜成分的改变,角膜神经异常和睑板腺功能障碍等。其中,免疫炎症反应是干眼发病机制中最为关键的环节,由眼表的天然免疫和获得性免疫反应共同调节。多种环境应激引发眼表天然免疫反应导致上皮细胞损伤和炎症,并激活获得性免疫参与眼表免疫炎症反应。目前已发现多种免疫细胞以及炎症因子参与了DE的发生和发展。本文就DE的免疫机制研究进展进行综述,并重点探讨获得性免疫在DE的启动与维持。通过分析最新观点和研究热点,我们对DE发病机制中的免疫调节机制进行了系统的介绍,并为DE的防治提供参考。     

氧化应激因素在干眼中的临床研究

干眼是由于泪液的量或质的异常引起的泪膜不稳定和眼表面的损害，从而导致眼不适症状的一类疾病。干眼与多种因素相关。本文主要探讨氧化应激因素对干眼的影响及临床治疗。针对氧化应激因素，干眼周期概念、干眼的眼表炎症和蛋白质组学相关研究证明了两者的相关性，有利于进行针对性临床治疗。针对氧化应激因素的治疗是干眼的潜在治疗方式，无防腐剂眼药水的使用、碘离子电渗疗法及其他蛋白质组学方法的临床试验证明了其合理性与有效性。随着近年来对抗老化药物、预防性整体健康以及环境科学作用的重视，对眼表氧化应激的研究可能会在未来几年产生越来越大的影响。     

氧化应激与糖尿病视网膜病变

糖尿病视网膜病变（DR）是严重的糖尿病眼部并发症之一。研究表明，氧化应激和应激激活的信号通路与DR有着密切关系。高糖通过多种机制刺激活性氧类物质的产生，从而生长因子和细胞因子的基因表达。正常情况下，过多的活性氧物质可被抗氧化防御系统清除，但持续性高血糖情况下过多的活性氧物质可导致细胞损害，包括视网膜内皮细胞、周细胞和视网膜节细胞。现就氧化应激在DR发生发展中所起的作用做一综述。     

The physiological and pathophysiological roles of the autophagy lysosomal system in the conventional aqueous humor outflow pathway: More than cellular clean up

During the last few years, the autophagy lysosomal system is emerging as a central cellular pathway with roles in survival, acting as a housekeeper and stress response mechanism. Studies by our and other labs suggest that autophagy might play an essential role in maintaining aqueous humor outflow homeostasis, and that malfunction of autophagy in outflow pathway cells might predispose to ocular hypertension and glaucoma pathogenesis. In this review, we will collect the current knowledge and discuss the molecular mechanisms by which autophagy does or might regulate normal outflow pathway tissue function, and its response to different types of stressors (oxidative stress and mechanical stress). We will also discuss novel roles of autophagy and lysosomal enzymes in modulation of TGFβ signaling and ECM remodeling, and the link between dysregulated autophagy and cellular senescence. We will examine what we have learnt, using pre-clinical animal models about how dysregulated autophagy can contribute to disease and apply that to the current status of autophagy in human glaucoma. Finally, we will consider and discuss the challenges and the potential of autophagy as a therapeutic target for the treatment of ocular hypertension and glaucoma.     

Therapeutic potential of iron chelators in retinal vascular diseases

Iron is one of the necessary metal elements in the human body. There are numerous factors that control the balance of iron metabolism, and its storage and transportation mechanisms are intricate. As one of the most energy-intensive tissues in the body, the retina is susceptible to iron imbalance. The occurrence of iron overload in the retina leads to the generation of a significant quantity of reactive oxygen species. This will aggravate local oxidative stress and inflammatory reactions and even lead to ferroptosis, eventually resulting in retinal dysfunction. The blood-retina-retinal barrier is eventually harmed by oxidative stress and elevated inflammation, which are characteristics of retinal vascular disorders. The pathophysiology of retinal vascular disorders may be significantly influenced by iron. Recently, iron-chelating agents have been found to have antioxidative and anti-inflammatory actions in addition to iron chelating. Therefore, iron neutralization is considered to be a new and potentially useful therapeutic strategy. This article reviews the iron overload in retinal vascular diseases and discusses the therapeutic potential of iron-chelating agents.