氧化应激及补体在年龄相关性黄斑变性发病中的作用机制

年龄相关性黄斑变性(AMD)是受环境和遗传因素共同影响的一种复杂疾病,目前已成为老年人最普遍的致盲原因之一。其发病机制与长期的慢性氧化应激及免疫炎症反应对组织的损伤密切相关。以下将氧化应激、补体及局部炎症在AMD发病中的作用机制作简要综述。     

补体因子H基因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, AMD)是50岁以上的人视力不可逆性损害的主要原因之一,遗传因素在AMD的发生、发展中起重要的作用。近年来研究发现,补体因子H( complement factor H,CFH)基因与AMD的发生有明显的相关性,现就补体因子H在老年黄斑变性中的研究进展进行综述。     

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。     

补体因子H基因在湿性年龄相关性黄斑变性治疗中的作用

年龄相关性黄斑变性(age-related macular degeneration,AMD)是一种与年龄、环境、基因相关的多因素退行性眼底病.补体因子H(complement factor H,CFH)是补体系统中重要的免疫抑制因子,其基因突变可导致CFH的免疫抑制作用减弱,在AMD发病中起一定的作用.CFH不仅与AMD易感性有关,而且在一定程度上影响湿性AMD抗血管内皮生长因子(vascular endothelial growth factor,VEGF)治疗后的视力提升.本文就CFH基因在湿性AMD发病机制中的作用及其对抗VEGF治疗效果的影响进行综述,为临床指导湿性AMD治疗预测AMD疗效提供新的思路.     

补体系统在老年性黄斑变性发病机制中的作用

补体系统是机体固有免疫的重要组成部分,包含分布于血浆中或细胞表面的40多种物质,可通过经典途径、凝集素途径或替代途径激活.补体系统通过炎症免疫、血管内皮生长因子表达上调、氧化应激等途径参与和影响老年性黄斑变性(AMD)的发生发展过程;其相关分子的基因多态性与AMD的易感性息息相关;靶向补体系统的治疗对AMD也有一定的疗效.补体系统与AMD相互关系的研究将有助于进一步阐明AMD的发病机制并为其治疗提供新的方向.     

凋亡在年龄相关性黄斑变性中的作用

目的：研究人类年龄相关性黄斑变性(AMD)中的凋亡。方法：研究死后的AMD视网膜及正常视网膜，用TUNEL检测死亡的细胞，以及用细胞特殊抗体的免疫细胞生化方法，确认杆细胞和锥细胞。切片还能标记Fas，Fas为一能激发其他类型细胞凋亡的表面受体。AMD的黄斑分为地图样萎缩(GA)和渗出性AMD2种类型。结果：与正常视网膜相比，AMD黄斑部的脉络膜内，视网膜色素上皮(RPE)、光感受器及内核层，TUNEL-阳性细胞数目的增加在统计学上有明显意义。在GA型AMD眼，TUNEL-阳性杆细胞及RPE细胞核出现于RPE萎缩的边缘。AMD患者黄斑部光感受器细胞Fas呈强阳性，而正常人光感受器细胞标记仅显示弱阳性。结论：本项研究证实，在人AMD中，RPE、光感受器细胞及内核层细胞以凋亡的过程死亡。在GA患眼中，大多数TUNEL-阳性RPE和光感受器细胞存在于萎缩区边缘，与临床所观察的伴有视力丧失的萎缩区扩展有关联。AMD患者光感受器细胞Fas标记的增加表示Fas／Fas配体系统参与光感受器细胞凋亡，此信息对AMD合理治疗的发展至关重要。     

炎症与年龄相关性黄斑变性

年龄相关性黄斑变性(AMD)是中老年人常见的致盲性眼病之一,特征性改变是玻璃膜疣(drusen)形成和脉络膜新生血管(CNV),确切发病机制不清,衰老、营养失衡和遗传等多种因素参与其发病。近年来研究发现机体慢性炎症和补体活化等免疫机制在其发病中占有重要作用,从AMD患者病灶组织及玻璃膜疣中发现有巨噬细胞和补体成分沉积,玻璃膜疣的形成与补体成分在Bruch膜上的活化以及脉络膜巨噬细胞吞噬功能下调有关,CNV的形成与补体成分活化、炎症刺激以及脉络膜巨噬细胞聚集活化有关,补体因子H的基因多态性也与AMD的发生有关。脂褐素碎片可刺激视网膜色素上皮细胞活化并分泌炎性细胞因子或血管生长因子,促进CNV的形成;长期光氧化损伤可导致视网膜蛋白变性形成新抗原,并刺激机体产生自身抗体,导致补体活化和巨噬细胞聚集,参与玻璃膜疣的形成和CNV发生。综上证据表明慢性炎症和补体活化等免疫学改变在AMD发生中起着重要作用,这就提示抗炎治疗可作为AMD患者的有效辅助治疗措施。     

补体在渗出型老年性黄斑变性中的作用研究进展

补体系统是机体免疫系统的重要组成部分,广泛参与机体抗微生物防御反应,清除凋亡细胞和免疫复合物以及维持组织稳态,进行免疫调节.补体系统与老年性黄斑变性(AMD)发生也密切相关.在玻璃膜疣中,含有多种选择激活途径中的蛋白;补体成分基因变异也使AMD的发病风险大大增加.补体系统多种分子与AMD CNV形成关系密切,针对补体系统异常激活的治疗可能为渗出型AMD的治疗带来新的曙光.     

脂褐素在年龄相关性黄斑变性发病中的作用

目前年龄相关性黄斑变性是影响老年人视力和生存质量的最重要致盲眼病之一,患病率逐年提高。由于对其确切发病机制不明,故缺乏有效的防治措施。近年来研究证明,脂褐素随年龄的增长沉积于视网膜下,通过慢性光化学作用造成视网膜色素上皮细胞功能异常,光感受器细胞变性增加,脉络膜新生血管形成,导致年龄相关性黄斑变性的发生。     

糖尿病对年龄相关性黄斑变性发生的影响

糖尿病导致的长期糖代谢紊乱可造成机体组织损伤,产生多种并发症.近年来研究者发现,糖尿病可能是年龄相关性黄斑变性的又一危险因素,其在改变血流动力学、增加氧化应激及加速糖基化终产物的累积方面等影响年龄相关性黄斑变性的疾病进程.根据目前有关糖尿病的流行病学研究资料和基础研究成果,有必要对糖尿病与年龄相关性黄斑变性的相关性研究进展进行综述.

Abstract：

Diabetes mellitus causing long term disturbed glucose metabolism could result in tissue injury and multiple complications. According to recent studies, diabetes mellitus might be regarded as one of the risk factors of age related macular degeneration (AMD). Diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. By studying epidemiological investigation and basic research on this subject comprehensively, it is required to review the correlation between diabetes mellitus and AMD.     

The complement system and age-related macular degeneration

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. There are increasing evidences to suggest the complement system may play a significant role on the pathogenesis of AMD. In this review, we summarise the current research in this area. METHODS: Review of literature. RESULTS: The complement system is a complex system with several activation pathways. Complement factor H (CFH) polymorphisms has been associated with increase risk of AMD. CFH is an inhibitor protein; the polymorphisms might cause uncontrolled activation by initiation events. CONCLUSION: Further studies on the molecular basis of the complement-mediated pathogenesis of AMD may offer novel therapy to AMD.     

Implications of genetic variation in the complement system in age-related macular degeneration

Age-related macular degeneration (AMD) is the main cause of vision loss among the elderly in the Western world. While AMD is a multifactorial disease, the complement system was identified as one of the main pathways contributing to disease risk. The strong link between the complement system and AMD was demonstrated by genetic associations, and by elevated complement activation in local eye tissue and in the systemic circulation of AMD patients. Several complement inhibitors have been and are being explored in clinical trials, but thus far with limited success, leaving the majority of AMD patients without treatment options to date. This indicates that there is still a gap of knowledge regarding the functional implications of the complement system in AMD pathogenesis and how to bring these towards clinical translation. Many different experimental set-ups and disease models have been used to study complement activation in vivo and in vitro, and recently emerging patient-derived induced pluripotent stem cells and genome-editing techniques open new opportunities to study AMD disease mechanisms and test new therapeutic strategies in the future. In this review we provide an extensive overview of methods employed to understand the molecular processes of complement activation in AMD pathogenesis. We discuss the findings, advantages and challenges of each approach and conclude with an outlook on how recent, exciting developments can fill in current knowledge gaps and can aid in the development of effective complement-targeting therapeutic strategies in AMD.     

Therapeutic targeting of the complement system in age-related macular degeneration: a review

The last decade has produced pivotal change in our understanding of the molecular mechanisms underlying age-related macular degeneration (AMD), a leading cause of global blindness. In this time, the complement system has featured as a unifying theme for several elements of new evidence: initially, the discovery of complement proteins within drusen and subsequently, the association between AMD and mutations in various complement pathway genes, most notably complement factor H. Increasingly, a wealth of data are pointing towards a role for chronic local inflammation and complement activation in the patho-aetiology of AMD. These findings have paved the way for the exploration of a new paradigm of therapy in AMD management; targeting of specific molecular constituents in the complement pathway thus producing dampening or inhibition of the inflammatory response. Such an approach has the potential to intervene earlier in the disease process and ideally before vision is compromised. In this review we discuss the role of the complement system in AMD, novel therapies in preclinical evaluation and clinical trial, and whether these have a part to play in reducing the burden of disease.     

miRNAs在年龄相关性黄斑变性的潜在作用

大量的研究证实miRNAs在病理性血管生成、氧化应激反应、免疫反应以及炎症等病理生理过程中扮演着重要的作用,而这些病理生理过程是老年性黄斑变性( age-related macular degeneration,AMD)的发生发展中的关键过程。本文综述了AMD发生的病理机制及miRNAs在调节这些病理机制中的作用,讨论了基于miRNAs治疗AMD的应用前景。     

The role of omega-3 and micronutrients in age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the United States, Europe, and other developed countries. Although the pathogenesis of AMD remains unclear, current evidence suggests a multifactorial aetiology. Nutrition may play an important role in the development and progression of AMD. There have been several epidemiological studies suggesting that omega-3 fatty acids could have a protective role in AMD, but a beneficial effect remains to be demonstrated in randomized controlled trials. There also exists a substantial body of evidence suggesting that protection against AMD may be provided by specific micronutrients (vitamins and minerals and antioxidants). The identification of risk factors for the development and progression of AMD is of particular importance for understanding the origins of the disorder and for establishing strategies for its prevention. We examine the relationship between dietary omega-3 intake and the incidence and progression of AMD, as well as the role of omega-3 supplementation in the prevention of the disorder, and also explore the role of other micronutrients in AMD.