Mechanisms of age-related ocular diseases: a comprehensive review with an emphasis on glaucoma

Reinehr, Sabrina; Köseoğlu, Ahmet Efe; Qin, Wanyun; Tsai, Teresa; Dick, H. Burkhard; Joachim, Stephanie C.*

Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Bochum, Germany

*Correspondence to: Stephanie C. Joachim, MD, stephanie.joachim@rub.de.

Abstract

With aging, senescence-related diseases are increasing in prevalence. The senescence of cells in the central nervous system has been linked with the development of neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease. These changes are not limited to the brain as many eye diseases, such as cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma, are also age-related. Among them, glaucoma is one of the leading causes of irreversible blindness with a multifactorial neurodegenerative nature. Besides an elevated intraocular pressure, an increased age is one of the main risk factors for this disease. Hence, in this review, we will discuss age-related changes in the context of eye disease, with a specific focus on glaucoma. Several general aging mechanisms were put forward in different eye diseases. This includes dysregulated nutrient sensing, cellular senescence, stem cell exhaustion, altered intercellular communication, genomic instability, telomere shortening, epigenetic alteration, loss of proteostasis, compromised autophagy, and mitochondrial dysfunction. In glaucoma, aging is a main risk factor for the development. This is triggered by oxidative, metabolic, immunological, and biomechanical stressors with many cross-talks. Oxidative stress, for example, can also trigger apoptotic cell death through mitochondrial damage, hypoxia, inflammation, and endothelial dysregulation. Also, with advanced age, alterations in extracellular matrix composition and structure are becoming important biomechanical contributing factors to the pathology of glaucoma. All mentioned mechanisms triggered by aging processes are generally accepted as contributing factors in the development of glaucoma in the aged eye. A better understanding of these will help to find novel therapeutic approaches for glaucoma patients in the future.

与年龄有关眼部疾病发病机制：以青光眼为重点的全面综述

摘要

中枢神经系统细胞的衰老与阿尔茨海默病或帕金森病等神经退行性疾病的发生有关。这些变化不仅限于大脑，许多眼部疾病，如白内障、糖尿病视网膜病变、老年性黄斑变性和青光眼，也与年龄有关。其中，青光眼是导致不可逆失明的主要原因之一，具有多因素神经退行性。除了眼压升高之外，年龄的增长也是导致这种疾病的主要风险因素之一。因此，此综述将讨论眼科疾病中与年龄有关的变化，并特别关注青光眼。在不同的眼科疾病中，提出了几种一般的衰老机制。其中包括营养传感失调、细胞衰老、干细胞衰竭、细胞间通信改变、基因组不稳定、端粒缩短、表观遗传改变、蛋白稳态丧失、自噬功能受损和线粒体功能障碍。衰老是青光眼发病的主要风险因素。这是由氧化、代谢、免疫和生物力学等多方面交叉作用的应激因素引发的。例如，氧化应激也会通过线粒体损伤、缺氧、炎症和内皮失调等方式引发细胞凋亡。此外，随着年龄的增长，细胞外基质组成和结构的改变也成为导致青光眼病理的重要生物力学因素。所有上述由衰老过程引发的机制都被普遍认为是导致老年性青光眼发生的因素。更好地了解这些机制将有助于在未来为青光眼患者找到新的治疗方法。