Common cell biologic and biochemical changes in aging and age-related diseases of the eye: toward new therapeutic approaches to age-related ocular diseases.
Common cell biologic and biochemical changes in aging and age-related diseases of the eye: toward new therapeutic approaches to age-related ocular diseases.
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DOI：
10.1167/iovs.13-12808
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发表时间：
2013-12
影响因子：
4.4
通讯作者：
E. Whitcomb;F. Shang;A. Taylor
中科院分区：
文献类型：
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作者：
E. Whitcomb;F. Shang;A. Taylor
对AMD、白内障和青光眼相关信息的回顾表明，虽然每个眼组织都有其自身的特征性代谢、结构和功能，但与年龄相关的功能障碍相关的稳态存在常见扰动。共同点似乎是生化应激及其后遗症。认识到年龄相关性虚弱的共同病因可以合理化可比较的风险因素-疾病发病率关系-例如AMD和白内障（以及心血管疾病和糖尿病）的营养风险因素-并告知潜在的新治疗途径，例如减压剂（即，抗氧化剂）和/或蛋白水解增强剂。它还最大限度地提高了研究工作和成本投资的回报。例如，预防AMD的药物或营养素也可以证明对白内障、青光眼或/和其他年龄相关的神经退行性疾病有效。本文综述了衰老和年龄相关性眼部疾病中细胞生物学和生化的变化。显然，这是一个更大的挑战，有更丰富的文献比可以适当地处理在一个简短的审查，如这一点。在这篇简短的评论中，我们关注与年龄有关的压力以及当前和预期的减轻压力的方法。认识到几乎所有与年龄相关的疾病如阿尔茨海默病和帕金森病、白内障、AMD、青光眼、糖尿病和过早衰老疾病如早衰症，都有受损蛋白质的积累，我们选择了大多数眼组织常见的与年龄相关的生物化学变化的三个方面：氧化应激;与在视网膜、透镜和角膜中积累的受损蛋白质相关和/或由于所述受损蛋白质引起的问题;以及细胞内降解能力，通常在生命早期或组织未受到压力时保持受损蛋白质的水平，但可能会在应力或老化时失效（图2和3）。1、2）.我们向研究人员道歉，我们没有引用他们的工作，或者只能通过评论来承认。图1慢性压力，保护能力，蛋白水解编辑机制和年龄相关疾病之间的拟议关系。当年轻时，蛋白质是完整的，细胞和组织功能保留。在暴露于各种应力（红色）时，包括...图2衰老时，蛋白质被破坏。这种损伤包括各种修饰，如氧化、与其他部分如糖衍生物反应、交联（黄色）和裂解。这些过程加速老化（遵循蓝线）和平行...许多社会中增长最快的部分是老年人。白内障、AMD和青光眼的患病率随着年龄的增长而加速。在75岁或以上的人群中，白内障、AMD和青光眼的患病率分别约为60%、15%和20%。对于年龄仅大10岁的人来说，这些估计几乎翻了一番。像大多数组织一样，大多数眼睛组织遭受受损蛋白质的积累。这种积累似乎涉及对蛋白质的合成后修饰以及对蛋白水解能力的限制，蛋白水解能力通常可以在改变或废弃的蛋白质转化为细胞毒性聚集体之前降解和去除它们。总的来说，我们把蛋白质的合成、合成后修饰、编辑和去除的总和称为“蛋白质修饰”。蛋白质缺乏也被认为是许多与年龄相关的神经病变和过早衰老综合征的病因。1 -7在此，我们从眼前部或角膜，通过透镜，再到后段或视网膜，回顾与年龄相关的变化和蛋白质质量控制的共同主题。
Reviews of information about AMD, cataract, and glaucoma make it apparent that while each eye tissue has its own characteristic metabolism, structure, and function, there are common perturbations to homeostasis that are associated with age-related dysfunction. The commonalities appeared to be biochemical stresses and their sequelae. Recognition of shared etiologic factors for age-related debilities allows rationalization of comparable risk factor-disease incidence relationships—such as nutritional risk factors for AMD and cataract (as well as cardiovascular disease and diabetes)—and informs about potential new therapeutic avenues, such as stress reducers (i.e., antioxidants) and/or proteolysis enhancers. It also maximizes the return on the investment in research effort and costs. For example, drugs or nutrients that protect against AMD may also prove effective against cataract, glaucoma, or/and other age-related neurodegenerative debilities. This article summarizes cell biologic and biochemical changes in aging and age-related diseases of the eye. Clearly, this is a larger challenge with a richer literature than can be properly treated in a short review such as this. In this short review, we focus on age-related stresses and current and anticipated means to diminish the stress. Recognizing that almost all age-related diseases such as Alzheimer and Parkinson diseases, cataract, AMD, glaucoma, diabetes, and the premature aging diseases such as progeria, have in common the accumulation of damaged proteins, we select three aspects of age-related biochemical changes that are common to most eye tissues: oxidative stresses; problems associated with and/or due to damaged proteins that accumulate in the retina, lens, and cornea; and intracellular degradative capacities that usually keep levels of damaged proteins in check in early life or when tissues are not stressed, but that may fail upon stress or aging (Figs. 1, ,2).2). We offer apologies to investigators whose work we do not cite or can acknowledge only via reviews.1 Figure 1 Scheme of proposed relationship between chronic stress, protective capacities, proteolytic editing machinery and age-related disease. When young, proteins are intact and cell and tissue functions are retained. Upon exposure to various stresses (red) including ... Figure 2 Upon aging, proteins are damaged. This damage includes various modifications such as oxidations, reaction with other moieties such as sugar derivatives, cross linking (yellow), and lysis. These processes accelerate upon aging (follow blue line) and parallel ... The most rapidly growing segment of many societies is the elderly. The prevalence of cataract, AMD, and glaucoma accelerates with age. Among those who are aged 75 years or older, prevalence rates of cataract, AMD, and glaucoma are approximately 60%, 15%, and 20% of the population, respectively. These estimates almost double for people aged just 10 years older. Like most tissues in general, most eye tissues suffer from the accumulation of damaged proteins. Such accumulation appears to involve post-synthetic modifications to proteins and limits on the proteolytic capacities that are normally available to degrade and remove the altered or obsolete proteins before they transform into cytotoxic aggregates. Collectively, we call the sum of synthesis, post-synthetic modification, editing and removal of proteins “proteopoise.” Compromises to proteopoise are also thought to be etiologic for many age-related neuropathies and premature aging syndromes.1–7 Herein, we work our way from the anterior of the eye, or cornea, through to the lens and on to the posterior segment or retina, recalling common themes of age-related changes and protein quality control.