PINK1/Parkin介导的线粒体自噬在眼科疾病中作用的研究进展

线粒体自噬作为一种选择性自噬过程,通过清除受损和多余线粒体来维持细胞正常生理功能。线粒体自噬与多种眼科疾病的发生发展有密切联系,而PINK1/Parkin信号通路作为线粒体自噬的主要通路之一,在白内障、青光眼、年龄相关性黄斑变性等多种眼科疾病中发挥了重要作用,靶向该通路的治疗手段也为多种眼科疾病的治疗提供了新思路。本文将对PINK1/Parkin介导的线粒体自噬通路在眼科疾病中的相关作用及机制进行综述,以期深入了解线粒体自噬在眼科相关疾病中的影响与价值。     

线粒体自噬信号通路在年龄相关性眼病中的研究进展

线粒体自噬是一种特殊形式的自噬,通过选择性清除功能失调和多余的线粒体,从而为细胞产生能量并调节能量稳态。同时,线粒体自噬具有促进细胞分化和延缓衰老等生理功能,其调控机制一旦失调或出现障碍将会导致生理性衰老和一系列与年龄相关的疾病发生。有研究发现,在多种年龄相关性眼病中存在着不同水平的线粒体自噬,如Fuchs内皮角膜营养不良、老年性白内障和原发性开角型青光眼等。本综述旨在概述线粒体自噬的相关信号通路及线粒体自噬在年龄相关性眼病中的研究进展。     

线粒体自噬参与糖尿病视网膜病变的研究进展

线粒体功能对于需氧真核细胞的生存至关重要,因为线粒体通过产生三磷酸腺苷(ATP)提供能量、调节细胞代谢、提供氧化还原平衡、参与免疫信号传导并启动细胞凋亡。线粒体自噬是一种细胞内针对功能障碍线粒体的选择性降解机制,参与线粒体的质量控制及细胞稳态的维持。近年来,越来越多的研究发现异常的线粒体自噬参与多种眼部疾病的发生发展,如糖尿病视网膜病变(DR)、年龄相关性黄斑变性和青光眼等。因此,本文总结已知的线粒体自噬定义,整理各种使用细胞培养、动物和人体组织模型进行研究的结果,并就线粒体自噬的分子生物学过程及其在DR中的作用展开综述,以期为DR的治疗手段提供新思路。     

miRNA调节自噬在眼科疾病中的应用

细胞自噬是一种通过溶酶体途径降解异常的细胞质蛋白和受损的细胞器的分解代谢过程,其过程失调已被发现与多种眼科疾病发生有关。微小RNA(miRNA)是一类非编码的内源性小分子RNA,其通过识别目的基因3’末端非翻译区来下调自噬相关基因及其调节因子表达。研究表明,miRNA表达异常可导致自噬失调,使miRNA成为治疗自噬失调相关的眼科疾病的潜在靶点。本文将对眼科疾病中有关miRNA参与细胞自噬调控的最新研究进展进行综述。     

自噬在视网膜和眼部疾病中的研究进展

自噬维持细胞内成分降解和再循环的稳态,是一种关键的细胞质量控制机制。在应激反应中,自噬促进细胞成分的降解,以提供细胞代谢所需的营养物质和能量。视网膜是眼睛中转导和处理视觉信息的光敏组织,对物质和能量需求极高,基础水平的自噬对维持视网膜细胞的稳态和视觉系统的正常功能至关重要。本文总结了自噬途径参与青光眼、年龄相关性黄斑变性、糖尿病视网膜病变、视网膜营养不良和视网膜脱离等眼科疾病的最新研究,为未来通过调控自噬治疗眼部疾病提供理论依据。     

自噬在眼部疾病中的研究进展

自噬是细胞对不良环境的一种自我防御机制,真核细胞通过自噬清除异常积聚的蛋白和损伤的或多余的细胞器,甚至病原微生物来维持细胞内稳态。近年来的研究表明,自噬与众多眼病包括白内障、角膜营养不良、青光眼、年龄相关性黄斑病变等疾病的发生和发展有着密切联系。期望通过小分子化合物（自噬的激活剂或抑制剂）或者药物调控细胞的自噬水平,从而为眼部疾病提供一种新的治疗策略。（国际眼科纵览,2015,39:309.314）     

TRPV4在眼科疾病中的研究进展

瞬态电位受体香草醛4(TRPV4)是一组存在于细胞膜上的非选择性阳离子通道。它们是调节细胞功能和信号通路的感觉信号的重要介质。TRPV4在眼部各种组织中广泛表达,可参与多种生理功能,包括渗透压调节、Ca²⁺稳态、凋亡和自噬,在正常生理功能以及不同病理中起重要作用。最近研究发现TRPV4与角膜上皮损伤、青光眼、年龄相关性白内障、糖尿病视网膜病变、早产儿视网膜病变、视网膜脱离等疾病紧密联系,调控着相关眼科疾病的发生和发展过程。本文就TRPV4通路在眼科疾病中的研究进展做简要综述,为临床眼病治疗提供思路。     

自噬在年龄相关性黄斑变性和视网膜脱离中的研究进展

自噬是维持细胞正常功能和内环境稳定的一种关键的自我保护机制,其在生长发育、适应、肿瘤抑制、老化、先天性和获得性免疫中扮演着重要角色.近年来的研究表明,自噬与众多眼病,如角膜营养不良、白内障、青光眼和视网膜疾病等的发生和发展有着密切联系.在年龄相关性黄斑变性(AMD)中,自噬异常损害视网膜色素上皮(RPE)细胞的功能,促进脂褐质形成并且参与玻璃膜疣的积累.在视网膜脱离(RD)中,自噬既能保护光感受器细胞,也能促进光感受器细胞的死亡.本文就自噬的分子机制、其在AMD和RD中的作用以及自噬作用的转变和水平的变化与损伤的时间、强弱及性质的相关性进行综述.     

细胞自噬在角膜疾病的研究进展

自噬是一种广泛存在于细胞内依赖于溶酶体的降解蛋白质的过程,通过清除细胞内一些受损的异常蛋白质和细胞器以维持细胞稳态。随着自噬在免疫防御、肿瘤、神经退行性变等方面越来越多地受到关注,自噬与眼病的关系也逐渐成为眼科基础研究的焦点。本文对自噬在角膜疾病方面的研究进展做一综述,以期为角膜疾病的治疗提供新的思路和方法。     

线粒体功能异常与青光眼的关系

线粒体既是细胞内能量转换器,又是决定细胞存活的重要因素。线粒体损伤、功能失调与多种神经元退行性变疾病发生发展均密切相关。青光眼为视神经病变的一种,近年来研究发现线粒体功能异常在其视神经损害过程,如氧化应激、谷氨酸兴奋性毒性、钙超载、机械压力、神经营养因子的剥夺、胶质细胞的激活等的病理机制中起着尤为重要的作用。本文对线粒体功能异常与青光眼关系的最新研究进展作以综述。（国际眼科纵览,2012,36：302-306）     

Autophagy in axonal degeneration in glaucomatous optic neuropathy

The role of autophagy in retinal ganglion cell (RGC) death is still controversial. Several studies focused on RGC body death, although the axonal degeneration pathway in the optic nerve has not been well documented in spite of evidence that the mechanisms of degeneration of neuronal cell bodies and their axons differ. Axonal degeneration of RGCs is a hallmark of glaucoma, and a pattern of localized retinal nerve fiber layer defects in glaucoma patients indicates that axonal degeneration may precede RGC body death in this condition. As models of preceding axonal degeneration, both the tumor necrosis factor (TNF) injection model and hypertensive glaucoma model may be useful in understanding the mechanism of axonal degeneration of RGCs, and the concept of axonal protection can be an attractive approach to the prevention of neurodegenerative optic nerve disease. Since mitochondria play crucial roles in glaucomatous optic neuropathy and can themselves serve as a part of the autophagosome, it seems that mitochondrial function may alter autophagy machinery. Like other neurodegenerative diseases, optic nerve degeneration may exhibit autophagic flux impairment resulting from elevated intraocular pressure, TNF, traumatic injury, ischemia, oxidative stress, and aging. As a model of aging, we used senescence-accelerated mice to provide new insights. In this review, we attempt to describe the relationship between autophagy and recently reported noteworthy factors including Nmnat, ROCK, and SIRT1 in the degeneration of RGCs and their axons and propose possible mechanisms of axonal protection via modulation of autophagy machinery.     

自噬在青光眼和视网膜退行性病变中的研究进展

自噬是细胞的管家程序,是细胞维持内环境稳定的必需途径。主要通过移除错误折叠的蛋白和损伤的细胞器来实现目的。自噬途径涉及到人体多种疾病,包括肿瘤、神经退行性疾病以及传染性疾病。神经退行性疾病与许多眼部疾病的病理机制密切相关,比如青光眼以及年龄相关性黄斑病变。此外,眼内细胞持续暴露于各种应激因子中,可导致自噬的发生,自噬通过回收利用代谢前体细胞,或者促进受损细胞的死亡来提高整体存活率。自噬与凋亡也被证实在不同的实验环境中存在协同和拮抗作用,而这一切与许多疾病的病理机制息息相关。本文对自噬的机制及调控进行了回顾,并总结了较新的有关青光眼中视网膜神经元自噬的理论以及运用自噬的治疗手段。     

Defects in retinal pigment epithelial cell proteolysis and the pathology associated with age-related macular degeneration

Maintenance of protein homeostasis, also referred to as “Proteostasis”, integrates multiple pathways that regulate protein synthesis, folding, translocation, and degradation. Failure in proteostasis may be one of the underlying mechanisms responsible for the cascade of events leading to age-related macular degeneration (AMD). This review covers the major degradative pathways (ubiquitin-proteasome and lysosomal involvement in phagocytosis and autophagy) in the retinal pigment epithelium (RPE) and summarizes evidence of their involvement in AMD. Degradation of damaged and misfolded proteins via the proteasome occurs in coordination with heat shock proteins. Evidence of increased content of proteasome and heat shock proteins in retinas from human donors with AMD is consistent with increased oxidative stress and extensive protein damage with AMD. Phagocytosis and autophagy share key molecules in phagosome maturation as well as degradation of their cargo following fusion with lysosomes. Phagocytosis and degradation of photoreceptor outer segments ensures functional integrity of the neural retina. Autophagy rids the cell of toxic protein aggregates and defective mitochondria. Evidence suggesting a decline in autophagic flux includes the accumulation of autophagic substrates and damaged mitochondria in RPE from AMD donors. An age-related decrease in lysosomal enzymatic activity inhibits autophagic clearance of outer segments, mitochondria, and protein aggregates, thereby accelerating the accumulation of lipofuscin. This cumulative damage over a person’s lifetime tips the balance in RPE from a state of para-inflammation, which strives to restore cell homeostasis, to the chronic inflammation associated with AMD.     

光诱导视网膜损伤在年龄相关性黄斑变性发病中的作用

年龄相关性黄斑变性发病机制与年龄、环境、遗传、氧化应激及炎性反应等因素密切相关.在光诱导视网膜损伤啮齿类动物中,眼底也表现出与年龄相关性黄斑变性类似的病理特征.光损伤会导致视网膜发生氧化应激、炎性反应、内质网应激、自噬及线粒体自噬、DNA损伤及细胞衰老、新生血管等病理性改变,进而损伤其结构与功能.     

Photoreceptor cell death and rescue in retinal detachment and degenerations

Photoreceptor cell death is the ultimate cause of vision loss in various retinal disorders, including retinal detachment (RD). Photoreceptor cell death has been thought to occur mainly through apoptosis, which is the most characterized form of programmed cell death. The caspase family of cysteine proteases plays a central role for inducing apoptosis, and in experimental models of RD, dying photoreceptor cells exhibit caspase activation; however, there is a paradox that caspase inhibition alone does not provide a sufficient protection against photoreceptor cell loss, suggesting that other mechanisms of cell death are involved. Recent accumulating evidence demonstrates that non-apoptotic forms of cell death, such as autophagy and necrosis, are also regulated by specific molecular machinery, such as those mediated by autophagy-related proteins and receptor-interacting protein kinases, respectively. Here we summarize the current knowledge of cell death signaling and its roles in photoreceptor cell death after RD and other retinal degenerative diseases. A body of studies indicate that not only apoptotic but also autophagic and necrotic signaling are involved in photoreceptor cell death, and that combined targeting of these pathways may be an effective neuroprotective strategy for retinal diseases associated with photoreceptor cell loss.